Techniques for percutaneous mitral valve replacement and sealing

ABSTRACT

An apparatus for use with a prosthetic heart valve at a native heart valve comprises an adjustable-lumen prosthetic valve support. In a delivery state, the prosthetic valve support is transluminally deliverable to the heart. The prosthetic valve support is transitionable, within the heart, into an implantation state for implantation at the native valve. In the implantation state, the prosthetic valve support has an inner edge that defines a lumen through the prosthetic valve support, the lumen having a first diameter. After the prosthetic valve support is implanted at the native valve, the prosthetic valve support is transitionable into an enlarged state in which the lumen has a second diameter that is greater than the first diameter. In the enlarged state, the prosthetic valve support is configured to support, at the native valve, the prosthetic heart valve within the lumen.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a Continuation of U.S. Ser. No. 16/045,059 to Grosset al., filed Jul. 25, 2018, which published as US 2018/0344457, andwhich is a Continuation of U.S. Ser. No. 15/213,791 to Gross et al.,filed Jul. 19, 2016 (now U.S. Pat. No. 10,245,143), and which is aContinuation of U.S. Ser. No. 14/237,264 to Gross et al., filed May 23,2014 (now abandoned), which published as US 2014/0324164, and which isthe US National Phase of PCT Application IL2012/000292 to Gross et al.,filed Aug. 5, 2012, which published as WO 2013/021374, and which

-   -   (1) claims priority from:        -   U.S. 61/515,372 to Gross et al., filed Aug. 5, 2011;        -   U.S. 61/525,281 to Gross et al., filed Aug. 19, 2011;        -   U.S. 61/537,276 to Gross et al., filed Sep. 21, 2011;        -   U.S. 61/555,160 to Gross et al., filed Nov. 3, 2011;        -   U.S. 61/588,892 to Gross et al., filed Jan. 20, 2012; and        -   U.S. Ser. No. 13/412,814 to Gross et al., filed Mar. 6,            2012, (now U.S. Pat. No. 8,852,272) all of which are            incorporated herein by reference; and    -   (2) is a Continuation-In-Part of U.S. Ser. No. 13/412,814 to        Gross et al., filed Mar. 6, 2012 (now U.S. Pat. No. 8,852,272).

This application is related to a PCT application to Gross et al.,entitled, “Percutaneous mitral valve replacement and sealing,” filedAug. 5, 2012, which was assigned application number IL2012/000293, andwhich published as WO 2013/021375.

FIELD OF THE INVENTION

Some applications of the present invention relate in general to valvereplacement. More specifically, some applications of the presentinvention relate to prosthetic valves for replacement of a cardiacvalve.

BACKGROUND

Ischemic heart disease causes regurgitation of a heart valve by thecombination of ischemic dysfunction of the papillary muscles, and thedilatation of the ventricle that is present in ischemic heart disease,with the subsequent displacement of the papillary muscles and thedilatation of the valve annulus.

Dilation of the annulus of the valve prevents the valve leaflets fromfully coapting when the valve is closed. Regurgitation of blood from theventricle into the atrium results in increased total stroke volume anddecreased cardiac output, and ultimate weakening of the ventriclesecondary to a volume overload and a pressure overload of the atrium.

SUMMARY OF THE INVENTION

For some applications of the invention, a prosthetic valve support isprovided for facilitating transluminal implantation of a prostheticvalve at a native valve (e.g., a native heart valve) of a subject. Theprosthetic valve support is configured to be placed at the native valve,such as by placing an upstream support portion (e.g., an annularportion) of the prosthetic valve support against an upstream surface ofthe native valve (e.g., against a native valve annulus). The prostheticvalve is subsequently implanted at the native valve by coupling theprosthetic valve to the prosthetic valve support, such as by expandingthe prosthetic valve in an opening defined by the prosthetic valvesupport. For some applications, the prosthetic valve support iscouplable to the native valve, independently of the prosthetic valve.The implantation of the prosthetic valve at the native valve replacesnative check valve functionality of the native valve with substitutecheck valve functionality of the prosthetic valve. For someapplications, the prosthetic valve support and/or the prosthetic valvecomprise tissue-engaging elements (e.g., support-anchoring elements, andvalve-anchoring elements, respectively), such as anchors or clips.

Typically, the prosthetic valve is expanded within one or more openingsdefined by the prosthetic valve support, and coupling of the prostheticvalve to the prosthetic valve support is facilitated byradially-expansive force applied by the prosthetic valve against theprosthetic valve support. For some applications, additional couplingtechniques, such as support-engaging elements, coupling leads, ratchetmechanisms, protrusions, and/or pockets are used.

For some applications, the prosthetic valve support is configured toreceive, at different periods, more than one prosthetic valve. Forexample, a first prosthetic valve may be removed from the prostheticvalve support, and replaced with a second prosthetic valve.Alternatively, the first prosthetic valve may be left in place when thesecond prosthetic valve is implanted. For example, the prosthetic valvesupport may define more than one lumen, each lumen configured to receivea respective prosthetic valve. Alternatively, the prosthetic valvesupport may define a lumen that is configured (e.g., shaped) to receivea first valve at a first period, and a second valve at a second period.

For some applications, the prosthetic valve support comprisessupport-anchoring elements that are flexibly-coupled to the upstreamsupport portion. For some such applications, the support-anchoringelements are configured to anchor the prosthetic valve support to thenative valve, while allowing the leaflets of the native valve tocontinue to function, at least in part. For some applications, theprosthetic valve support comprises support-anchoring elements whoselength is variable (e.g., adjustable).

For some applications of the invention, a cross-sectional area of theopening defined by the prosthetic valve support is adjustable.

For some applications of the invention, delivery apparatus forimplantation of a medical device (e.g., a prosthetic valve and/or aprosthetic valve support) is provided, the delivery apparatus and/or themedical device being configured to allow retrievability of the medicaldevice during one or more stages of delivery and/or deployment of themedical device.

There is Therefore Provided, in Accordance with an Application of thePresent Invention, Apparatus for Use with a First Prosthetic Valve and aSecond Prosthetic Valve at a Native Heart Valve of a Subject, theApparatus Including:

-   -   a prosthetic valve support, shaped to define at least one lumen,        and configured:        -   to be implanted at the native valve,        -   to facilitate, at a first period, implantation at the native            valve of the first prosthetic valve, and        -   to facilitate, at a second period, implantation at the            native valve of the second prosthetic valve without removal            of the first valve.

In an application, the prosthetic valve support is configured tofacilitate the implantation of the first prosthetic valve by beingconfigured to receive the first prosthetic valve in the at least onelumen.

In an application, the prosthetic valve support includes a seal, which:

does not cover at least a first region of the at least one lumen,

covers at least a second region of the at least one lumen, and

is configured to be openable at at least the second region,

and the prosthetic valve support is configured:

to facilitate the implantation of the first prosthetic valve by beingconfigured to receive the first prosthetic valve in the first region,and

to facilitate the implantation of the second prosthetic valve by beingconfigurable, by opening of the seal, to receive the second prostheticvalve in the second region.

In an application, the at least one lumen is shaped to define at least afirst lumen and a second lumen, and the seal covers the second lumen.

In an application, the first region and the second region are defined bythe same lumen.

In an application, the apparatus includes a covering that covers theprosthetic valve support, and the seal is defined by a portion of thecovering.

In an application, the prosthetic valve support is configured to receivethe first prosthetic valve in the lumen, and is configured to facilitatethe implantation of the second prosthetic valve by being configured toreceive the second prosthetic valve in the same lumen.

In an application, the apparatus further includes the first and secondprosthetic valves, the first prosthetic valve defines a lumentherethrough, and the second prosthetic valve is configured to beimplanted in the lumen of the first prosthetic valve.

In an application:

the second prosthetic valve defines a lumen therethrough,

after the first period, and before the second period, the lumen of thefirst prosthetic valve has a first diameter, and

the prosthetic valve support is configured such that, after the secondperiod, the lumen of the second prosthetic valve has a diameter that isat least as great as the first diameter.

In an application, the prosthetic valve support is configured such that,after the second period, the lumen of the second prosthetic valve has adiameter that is greater than the first diameter.

In an application, the prosthetic valve support includes a weak zonethat circumscribes and defines the lumen, and is configured tofacilitate enlarging of the lumen.

In an application, the prosthetic valve support is configured tofacilitate enlarging of the lumen by being configured to be deformed bya radially-expansive force applied from within the lumen.

In an application, the prosthetic valve support includes a cylindricalelement:

shaped to define the lumen,

configured to receive the first prosthetic valve at a first portion ofthe lumen, and

configured to receive the second prosthetic valve support at a secondportion of the lumen.

In an application, the cylindrical element is configured to receive thefirst prosthetic valve at a first longitudinal portion of the lumen, andto receive the second prosthetic valve at a second longitudinal portionof the lumen.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a prosthetic heart valve forimplantation at a native heart valve of a subject, the apparatusincluding:

a core, shaped to define at least one conduit therethrough; and

one or more control filaments, slidable through the conduit, andreversibly couplable to the prosthetic valve,

the apparatus being configured such that sliding the control filamentsin a first direction through the conduit facilitates expansion of theprosthetic valve, and sliding the control filaments in a seconddirection through the conduit facilitates compression of the prostheticvalve.

In an application, the apparatus is configured such that sliding thecontrol filaments in the first direction through the conduit facilitatesradial expansion of the prosthetic valve away from the core.

In an application, the apparatus further includes the prosthetic valve,a delivery tube and a pushing member, and:

the prosthetic valve has an expanded configuration and a compressedconfiguration,

the delivery tube is configured to be transluminally delivered to thenative valve,

the pushing member includes the core,

the pushing member is configured:

-   -   to be disposed within the delivery tube,    -   to be fixedly coupled, within the delivery tube, to the        prosthetic valve in the compressed configuration thereof,    -   when fixedly coupled to the prosthetic valve, to facilitate        movement of the prosthetic valve with respect to the delivery        tube, and    -   to be decouplable from the prosthetic valve.

In an application, the apparatus further includes one or more releasewires, configured to facilitate decoupling of the control filaments fromthe prosthetic valve.

In an application, the apparatus further includes one or more guideelements, radially extendable from the core, and configured to guideexpansion of the prosthetic valve away from the core.

In an application, the guide elements are configured to automaticallyradially retract when the control filaments are decoupled from theprosthetic valve.

There is further provided, in accordance with an application of thepresent invention, apparatus for use at a native heart valve of asubject, the apparatus including:

a prosthetic valve, configured to be transluminally delivered to, andimplantable at, the native valve of the subject;

a prosthetic valve support, configured to be transluminally delivered tothe native valve of the subject, and to facilitate implantation of theprosthetic valve;

at least one coupling lead, extending between the prosthetic valve andthe prosthetic valve support; and

a ratchet housing, slidably coupled to the coupling lead, and configuredto be slidable over the coupling lead in a first direction, andinhibited from sliding over the coupling lead in an opposite direction,

the apparatus being configured such that sliding of the ratchet housingover the coupling lead in the first direction facilitates coupling ofthe prosthetic valve to the prosthetic valve support.

In an application, the coupling lead extends between a proximal portionof the prosthetic valve, and the prosthetic valve support.

In an application, the prosthetic valve support includes one or moresupport-anchoring elements, configured to couple the prosthetic valvesupport to the native valve, and the coupling lead extends between theprosthetic valve and the support-anchoring elements.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a native heart valve of asubject, the apparatus including:

a first expandable prosthetic valve component, including a crimpableframe, and configured to be transcatheterally advanceable toward thenative valve while the first prosthetic valve component is in a crimpedstate thereof;

a second expandable prosthetic valve component, including a crimpableframe, and configured to be transcatheterally advanceable toward thenative valve, placeable in the native valve while the second prostheticvalve component is in a crimped state thereof, and couplable to thefirst prosthetic valve component, expansion of the second prostheticvalve component facilitating coupling of the second prosthetic valvecomponent to the first prosthetic valve component; and

one or more tissue-engagement elements, coupled to at least one of theprosthetic valve components, the tissue-engagement elements configured,when the prosthetic valve component is in an expanded state thereof, toextend from the prosthetic valve component, and to inhibit a proximalmovement of the prosthetic valve component.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a prosthetic valve forimplantation at a native valve of a subject, the native valve (1)defining an orifice, (2) including at least one native leaflet, having anative beating, and (3) having a native blood flow regulationfunctionality, the apparatus including:

-   -   a prosthetic valve support, including:    -   an upstream support portion, configured to be placed against an        upstream side of the native valve, to have an inner perimeter        that defines an opening that is configured to receive the        prosthetic valve, and        -   at least one clip, configured to be coupled to a native            leaflet of the native valve, the clip including a plurality            of clip arms, at least one clip arm coupled to a            clip-controller interface; and    -   a clip controller, couplable to the clip-controller interface,        and configured to control a relative angular disposition between        the clip arms.

For some applications, techniques described herein are practiced incombination with techniques described in one or more of the referencescited in the Background section and Cross-references section of thepresent patent application.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-H are schematic illustrations of sequential steps in theimplantation of an implant comprising a prosthetic valve and aprosthetic valve support, in accordance with some applications of thepresent invention;

FIG. 2 is a schematic illustration of a prosthetic valve support,comprising adjustable prosthetic valve support, in accordance with someapplications of the invention;

FIG. 3 is a schematic illustration of a prosthetic valve support,comprising an adjustable prosthetic valve support, in accordance withsome applications of the invention;

FIG. 4 is a schematic illustration of a prosthetic valve support,comprising an adjustable prosthetic valve support, in accordance withsome applications of the invention;

FIG. 5 is a schematic illustration of a prosthetic valve support,comprising a graduated prosthetic valve support, in accordance with someapplications of the invention;

FIG. 6 is a schematic illustration of a prosthetic valve support,comprising a flexibly-anchored prosthetic valve support, in accordancewith some applications of the invention;

FIG. 7 is a schematic illustration of a prosthetic valve support,comprising a flexibly-anchored prosthetic valve support, in accordancewith some applications of the invention;

FIGS. 8A-B are schematic illustrations of a prosthetic valve support,and a prosthetic valve, the prosthetic valve comprising anintegrally-anchoring prosthetic valve, in accordance with someapplications of the invention;

FIGS. 9A-E are schematic illustrations of delivery apparatus, used todeploy a medical device, in accordance with some applications of theinvention;

FIG. 10 is a schematic illustration of a prosthetic valve support,comprising a multi-lumen prosthetic valve support, in accordance withsome applications of the invention;

FIG. 11 is a schematic illustration of a prosthetic valve, comprising anextended-lumen prosthetic valve support, in accordance with someapplications of the invention;

FIGS. 12A-B are schematic illustrations of a prosthetic valve support,comprising an adjustable-lumen prosthetic valve support, in accordancewith some applications of the invention;

FIGS. 13A-D are schematic illustrations of a prosthetic valve support,comprising an asymmetric prosthetic valve support, in accordance with anapplication of the invention;

FIG. 14 is a schematic illustration of a prosthetic valve support, inaccordance with some applications of the invention;

FIGS. 15A-E are schematic illustrations of the implantation of aprosthetic valve support and a prosthetic valve, in accordance with someapplications of the invention;

FIG. 16 is a schematic illustration of a prosthetic valve support beingdeployed in a native heart valve, in accordance with some applicationsof the invention;

FIGS. 17A-D are schematic illustrations of prosthetic valve supports,comprising tissue-engaging elements, which comprise support-anchoringelements, comprising length-adjustable holding elements, in accordancewith some applications of the invention;

FIGS. 18A-B are schematic illustrations of prosthetic valve supports,comprising tissue-engaging elements, which comprise support-anchoringelements, comprising length-adjustable holding elements, in accordancewith some applications of the invention;

FIG. 19 is a schematic illustration of a prosthetic valve support,comprising tissue-engaging elements, which comprise support-anchoringelements, comprising length-adjustable holding elements, in accordancewith some applications of the invention;

FIGS. 20A-F are schematic illustrations of prosthetic valve supports,comprising tissue-engaging elements, which comp support-anchoringelements, comprising flexible support-anchoring elements, in accordancewith some applications of the invention;

FIGS. 21A-C are schematic illustrations of a prosthetic valve support,comprising an inflatable support-engaging element, in accordance withsome applications of the invention;

FIGS. 22A-C are schematic illustrations of sequential steps in theimplantation of an implant, comprising a prosthetic valve and aprosthetic valve support, coupled via coupling leads;

FIGS. 23A-B are schematic illustrations of a prosthetic valve support,shaped to define at least one pocket, and the coupling thereto of aprosthetic valve, in accordance with some applications of the invention;

FIG. 24 is a schematic illustration of a prosthetic valve support,shaped to define at least one pocket, and the coupling thereto of aprosthetic valve, in accordance with some applications of the invention;

FIGS. 25A-E are schematic illustrations of a retrieval device, andsequential steps in the use thereof, in accordance with someapplications of the invention;

FIGS. 26A-C are schematic illustrations of a prosthetic valve supportcomprising a braided structure, and the deployment thereof, inaccordance with some applications of the invention;

FIGS. 27A-D are schematic illustrations of delivery apparatus, inaccordance with some applications of the invention;

FIGS. 28A-D are schematic illustrations of the deployment of aprosthetic valve in the lumen of another prosthetic valve, in accordancewith some applications of the invention;

FIGS. 29A-F are schematic illustrations of the deployment of aprosthetic valve in the lumen of another prosthetic valve, and of aprosthetic valve support configured to facilitate such deployment, inaccordance with some applications of the invention;

FIGS. 30A-B are schematic illustrations of the deployment of a secondprosthetic valve in the lumen of a prosthetic valve support, in which afirst prosthetic valve is already disposed, in accordance with someapplications of the invention;

FIGS. 31A-C are schematic illustrations of a flexible delivery tube,configured to facilitate removal thereof from a subject, in accordancewith some applications of the invention;

FIGS. 32A-C are schematic illustrations of a compressible delivery tube,configured to facilitate removal thereof from a subject, in accordancewith some applications of the invention;

FIGS. 33A-C are schematic illustrations of a dismantling delivery tube,configured to facilitate removal thereof from a subject, in accordancewith some applications of the invention;

FIG. 34 is a schematic illustration of a prosthetic valve, comprising aleaflet-engaging element, in accordance with some applications of theinvention;

FIGS. 35A-C are schematic illustrations of a prosthetic valve supportcomprising temporary valve components, and sequential steps in thecoupling of a prosthetic valve to the support, in accordance with someapplications of the invention;

FIGS. 36A-D are schematic illustrations of a prosthetic valve support,comprising support-anchoring elements and stabilizing legs, inaccordance with some applications of the invention;

FIGS. 37A-H are schematic illustrations of a prosthetic valve support,comprising support-anchoring elements and stabilizing legs, andsequential steps in the implantation thereof, in accordance with someapplications of the invention;

FIGS. 38A-H are schematic illustrations of a prosthetic valve support,comprising support-anchoring elements and stabilizing legs, andsequential steps in the implantation thereof, in accordance with someapplications of the invention;

FIGS. 39A-D are schematic illustrations of a medical device, comprisingone or more coupling tabs, in accordance with some applications of theinvention;

FIGS. 40A-C are schematic illustrations of a prosthetic valve,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 41A-B are schematic illustrations of a prosthetic valve, and aprosthetic valve support, comprising support-anchoring elements that arecouplable to the prosthetic valve, in accordance with some applicationsof the invention;

FIGS. 42A-B are schematic illustrations of a prosthetic valve, and aprosthetic valve support, comprising support-anchoring elements that arecouplable to the prosthetic valve, in accordance with some applicationsof the invention;

FIGS. 43A-C are schematic illustrations of a prosthetic valve, and aprosthetic valve support, comprising support-anchoring elements that arecouplable to the prosthetic valve, in accordance with some applicationsof the invention;

FIGS. 44A-B are schematic illustrations of a prosthetic valve support,comprising support-anchoring elements, and a prosthetic valve,comprising valve-anchoring elements that are couplable to thetissue-engaging elements of the prosthetic valve support, in accordancewith some applications of the invention;

FIGS. 45A-C are schematic illustrations of a lock for facilitatingdelivery of a medical device, in accordance with some applications ofthe invention;

FIGS. 46A-B are schematic illustrations of a prosthetic valve support,comprising one or more support-anchoring elements, coupled to astabilizing strip, in accordance with some applications of theinvention;

FIGS. 47A-C are schematic illustrations of sequential steps in theimplantation of an implant, comprising a prosthetic valve and aprosthetic valve support, in accordance with some applications of theinvention;

FIGS. 48A-C are schematic illustrations of sequential steps in theimplantation of an implant, comprising a prosthetic valve and aprosthetic valve support, in accordance with some applications of theinvention;

FIG. 49 is a schematic illustration of the prosthetic valve support, inaccordance with some applications of the invention;

FIG. 50 is a schematic illustration of a step in the implantation of theimplant, in accordance with some applications of the invention;

FIGS. 51A-B are schematic illustrations of the prosthetic valve support,in accordance with some applications of the invention;

FIG. 52 is a schematic illustration of the prosthetic valve, inaccordance with some applications of the invention;

FIGS. 53A-C are schematic illustrations of the prosthetic valve,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 54A-D are schematic illustrations of the prosthetic valve,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 55A-E are schematic illustrations of the prosthetic valve,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 56A-D are schematic illustrations of the prosthetic valve,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 57A-D are schematic illustrations of the prosthetic valve,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 58A-D are schematic illustrations of the prosthetic valve support,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 59A-B are schematic illustrations of the prosthetic valve support,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 60A-B are schematic illustrations of the prosthetic valve support,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 61A-C are schematic illustrations of the prosthetic valve support,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIGS. 62A-D are schematic illustrations of a delivery device for thedelivery and deployment of an expandable medical device, in accordancewith some applications of the invention;

FIGS. 63A-B are schematic illustrations of the delivery device for thedelivery and deployment of an expandable medical device, in accordancewith some applications of the invention;

FIGS. 64A-C, 65A-B, 66A-B, and 67A-B are schematic illustrations of alocking mechanism for delivery of an expandable medical device, inaccordance with some applications of the invention;

FIGS. 68A-B and 69A-E are schematic illustrations of a retrievableprosthetic valve support, and sequential steps in the retrieval of theretrievable prosthetic valve support, in accordance with someapplications of the invention;

FIGS. 70A-C are schematic illustrations of the prosthetic valve,comprising tissue-engaging elements, in accordance with someapplications of the invention;

FIG. 71 is a schematic illustration of an implant comprising aprosthetic valve and a prosthetic valve support, in accordance with someapplications of the present invention;

FIGS. 72A-D are schematic illustrations of an implant, comprising aprosthetic valve support and a prosthetic valve, in accordance with someapplications of the invention;

FIG. 73 is a schematic illustration of a prosthetic valve support, foruse with a prosthetic valve, in accordance with some applications of theinvention;

FIGS. 74A-L are schematic illustrations of steps in the implantation ofan implant, comprising a prosthetic valve and a prosthetic valvesupport, in a native valve of a subject, in accordance with someapplications of the invention;

FIGS. 75A-D are schematic illustrations of an implant, comprising aprosthetic valve support and a prosthetic valve, and steps in theimplantation thereof, in accordance with some applications of theinvention;

FIGS. 76A-F are schematic illustrations of steps in the implantation ofan implant, comprising a prosthetic valve and a prosthetic valvesupport, in a native valve of a subject, in accordance with someapplications of the invention;

FIG. 77 is a schematic illustration of an implant, implanted at themitral valve of a subject, in accordance with some applications of theinvention;

FIG. 78 is a schematic illustration of an implant, implanted at thetricuspid valve of a subject, in accordance with some applications ofthe invention;

FIG. 79 is a schematic illustration of an implant, implanted at thepulmonary valve of a subject, in accordance with some applications ofthe invention; and

FIG. 80 is a schematic illustration of an implant, implanted at theaortic valve of a subject, in accordance with some applications of theinvention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 1A-H, which are schematic illustrations ofsequential steps in the implantation in a native heart valve 23 of theheart 22 of a subject 20 of an implant 30, comprising (1) a firstprosthetic valve component, i.e., prosthetic valve support 40, and (2) asecond prosthetic valve component, i.e., a prosthetic valve 42, inaccordance with some applications of the present invention. For suchapplications of the present invention, native valve 23 includes a nativemitral valve 24 by way of illustration and not limitation; the scope ofthe present invention includes implanting implant 30 in other valves ofthe heart (e.g., the tricuspid valve, the pulmonary valve, or the aorticvalve). FIG. 1A illustrates a cross-section through heart 22 of thesubject which is used throughout FIGS. 1B-G to illustrate theimplantation procedure. As shown in the cross-sectional illustration,native mitral valve 24 includes native leaflets 82, which are supportedby native chordae tendineae 80.

FIG. 1B shows prosthetic valve support 40 being deployed in a leftatrium 26. Prior to deployment, support 40 is percutaneously (e.g.,transcatheterally) advanced into left atrium 26, typically via overtube44. In some applications of the present invention, the advancement ofovertube 44 toward heart valve 23 is preceded by advancement of aguidewire 45 through vasculature of the subject. Typically, guidewire 45is used to guide overtube 44 through the vasculature. During itsdeployment, support 40 is moved distally (e.g., by a pushing couplingelement, not shown for clarity of illustration and describedhereinbelow), such that support 40 emerges from the distal end ofovertube 44. Support 40 is typically expandable, and typically comprisesa wire frame which comprises a shape-memory material such as, but notlimited to, nickel titanium (nitinol). For some applications of theinvention, support 40 comprises nickel cobalt, stainless steel and/ortitanium. As support 40 gradually emerges from overtube 44, it graduallyexpands to assume an expanded configuration.

FIG. 1C shows support 40 reversibly coupled to one or more holdingmembers 46, which exert a distal pushing force that causes support 40 toemerge from within overtube 44. Once fully exposed from within overtube44, support 40 expands to assume the expanded configuration, as shown.In its expanded state, support 40 is annular and is shaped so as todefine a lumen therethrough. Typically, prosthetic valve support 40 isshaped to define an outer edge 69 and an inner edge 68 (see FIG. 1H).Outer edge 69 typically defines the diameter of the annular prostheticvalve support, and inner edge 68 typically defines the diameter of thelumen in which prosthetic valve 42 is typically disposed. As shown inFIG. 1C, once support 40 is fully exposed from within overtube 44,holding members 46 continue to push support 40 distally (i.e., in thedirection as indicated by the arrows) until support 40 is positionedagainst an annulus of native heart valve 23.

Support 40 is held against the annulus of native valve 23 (e.g., byholding members 46) such that the lumen of support 40 aligns with thelumen of the native valve, and such that atrium 26 and ventricle 28remain in fluid communication.

Following the positioning of support 40 against the annulus of thenative valve, prosthetic valve 42 is percutaneously (e.g.,transcatheterally) advanced and delivered toward the native valve,typically along guidewire 45, as shown in FIG. 1D.

Prosthetic valve 42 is typically expandable, and typically comprises awire frame which comprises a shape-memory material such as, but notlimited to, nickel titanium (nitinol). For some applications of theinvention, prosthetic valve 42 comprises nickel cobalt, stainless steeland/or titanium. During the advancing, prosthetic valve 42 is disposedin a distal portion of a delivery tube 60, which holds the prostheticvalve in a compressed (e.g., crimped) configuration. Delivery tube 60 isslidably advanceable within overtube 44. Prosthetic valve 42 istypically delivered through the native valve and into ventricle 28, asshown in FIG. 1D. Typically, prosthetic valve 42 is delivered to thenative valve while support 40 is held against the annulus of nativevalve 23 by holding members 46.

FIG. 1E shows prosthetic valve 42 being partially deployed from withindelivery tube 60. As prosthetic valve 42 expands, prosthetic valve 42expands toward assuming an expanded configuration. Prosthetic valve 42comprises a primary structural element 130, which is typicallycylindrical, prismatic, or any other suitable shape, and is shaped so todefine a lumen. Prosthetic valve components (e.g., leaflets; not shownfor clarity of illustration) are typically disposed within the lumen ofthe prosthetic valve, are coupled to a surface of structural element 130defining the lumen, and regulate blood flow therethrough.

Typically, a plurality of tissue-engaging elements 62 are disposed at adistal portion of the primary structural element 130 of prosthetic valve42. For applications in which prosthetic valve 42 comprisestissue-engaging elements 62, tissue-engaging elements 62 comprisevalve-anchoring elements 64. For such applications of the presentinvention, primary structural element 130 of prosthetic valve 42 isgenerally cylindrical (e.g., shaped so as to define a right circularcylinder), and anchoring elements 64 protrude radially from a surface ofthe cylinder. It is to be noted that although prosthetic valve 42 isshown comprising tissue-engaging elements 62, the scope of the presentapplication includes prosthetic valves with no tissue-engaging elements62.

FIG. 1F shows prosthetic valve 42 being moved proximally, such that atleast part of primary structural element 130 is disposed in therespective lumens of native valve 23 and prosthetic valve support 40,and such that valve-anchoring elements 64 contact the ventricular sideof the native valve. Such contacting of elements 64 with the ventricularside of the native valve restricts further undesired atrial (i.e.,proximal) movement of the prosthetic valve. Typically, the contactbetween valve-anchoring elements 64 and the ventricular side of thenative valve occurs by valve-anchoring elements 64 protruding betweenchordae tendineae 80 and capturing leaflets 82 of the native valve.Responsively to the capturing by valve-anchoring elements 64, leaflets82 are typically pushed proximally and/or outward by the prostheticvalve. In some applications of the invention, leaflets 82 are heldagainst the outer surface of primary structural element 130 byvalve-anchoring elements 64, so as to reduce blood flow between nativeleaflets 82 and prosthetic valve 42. In an alternative application ofthe invention, rather than being partially deployed in the ventricle andsubsequently moved proximally (as described with reference to FIGS.1E-F), prosthetic valve 42 is deployed directly in the lumen of thenative valve.

Following the capturing of native leaflets 82, prosthetic valve 42 isthen fully exposed from within delivery tube 60 (by pushing valve 42relative to delivery tube 60 or by retracting delivery tube 60 withrespect to valve 42) and is allowed to expand further. FIG. 1G showsprosthetic valve 42 in a deployed and expanded configuration after beingfully exposed from within delivery tube 60. The expansion of prostheticvalve 42 exerts a radial force against support 40, thereby facilitatingcoupling of prosthetic valve 42 to support 40. Implant 30, comprisingprosthetic valve 42 and support 40, is secured in place by sandwichingthe native valve by the components of implant 30. That is, (1) implant30 is inhibited from ventricular (i.e., distal) movement by support 40and the radial force of prosthetic valve 42 exerted on support 40, and(2) implant 30 is inhibited from atrial (i.e., proximal) movement byvalve-anchoring elements 64.

For some applications of the present invention, support 40 preventsvalve 42 from expanding to assume a fully-expanded configuration (i.e.,a configuration to which valve 42 would otherwise expand without beingimpeded by support 40 or tissue). In such applications, the radial forceexerted by support 40 on valve 42 facilitates coupling and sealingbetween support 40 and valve 42 (for example, by increasing frictionbetween support 40 and valve 42), and facilitates implantation ofimplant 30 at native valve 23.

FIG. 1H shows implant 30 following implantation in the mitral valve ofthe subject. This figure is a transverse atrial cross-section, showingprosthetic valve support 40 in contact with the atrial side of thenative valve. Prosthetic valve 42 is expanded, and is disposed in, andcoupled to, prosthetic valve support 40. Tissue-engaging elements 62,comprising valve-anchoring elements 64, are disposed on the ventricularside of the native valve (as described hereinabove with reference toFIGS. 1F-G), and are therefore illustrated in phantom. Valve-anchoringelements 64 are typically arranged in two clusters, each cluster beingdisposed on opposite sides of prosthetic valve 42.

Typically, when deployed as shown, prosthetic valve 42 is configured tobe aligned with the native valve such that valve-anchoring elements 64protrude toward, and engage leaflets 82 of the native valve. In someapplications of the present invention, valve-anchoring elements 64protrude toward, and engage, commissures 84 of the native valve. In someapplications of the invention, a single valve-anchoring element 64 isdisposed on each side of the prosthetic valve. It is to be noted thatthe scope of the present application includes any other suitablearrangement of valve-anchoring elements 64 with respect to valve 42.Typically, valve-anchoring elements 64 capture leaflets 82 of the nativevalve, holding them clear of the flow of blood through the prostheticvalve and the left ventricular outflow tract (LVOT).

For clarity of illustration, the lumen defined by prosthetic valve 42 isshown as being empty, such that ventricle 28 is visible. However, asdescribed hereinabove, prosthetic valve 42 typically comprises valvecomponents (e.g., prosthetic valve leaflets, not shown in FIG. 1H), thatare disposed in the lumen of prosthetic valve 42, coupled to structuralelement 130, and configured to regulate blood flow through prostheticvalve 42.

Reference is again made to FIGS. 1A-H. For some applications, asdescribed hereinabove, valve-anchoring elements 64 function so as to (1)prevent proximal migration of prosthetic valve 42 into the subject'satrium, while (2) creating a seal between the native valve 23 andprosthetic valve 42 by generally clamping native leaflets 82 betweenvalve-anchoring elements 64 and primary structural element 130, valvesupport 40, and/or native valve annulus.

For other applications, prevention of proximal migration of valve 42 ismaintained, while movement of native leaflets 82 with respect toprosthetic valve 42 is allowed. For example, valve-anchoring elements 64may have the aforementioned functionalities by having lengths of lessthan 5 mm, and/or by having a total width of each cluster ofvalve-anchoring elements (corresponding to respective leaflets of thenative valve) being less than 5 mm. For example, the valve may include asingle valve-anchoring element 64 corresponding to each leaflet of thenative valve, the width of each of the single valve-anchoring elementsbeing less than 1 mm. Thus, the valve may be stopped from proximallymigrating into the atrium by the valve-coupling elements preventing thedistal end of the valve from migrating further proximally than edges ofnative leaflets of the valve. Furthermore, the valve-anchoring elementsmay allow movement of the native leaflets with respect to the prostheticvalve by not generally squeezing the native leaflets between thevalve-coupling elements and primary structural element 130 of theprosthetic valve. In other applications of the invention, prostheticvalve support 40 comprises support-anchoring elements (such as clips),and is directly coupled to the native valve. For some such applications,no valve-anchoring elements are used; rather, implant 30 is coupled tothe native valve via prosthetic valve support 40 (e.g., as describedhereinbelow, such as with reference to FIGS. 37A-H and 38A-H). For someapplications, both valve-anchoring elements and support-anchoringelements are used. For some applications, by allowing movement of thenative leaflets with respect to the prosthetic valve, sealing of thenative leaflets against the outer surface of the primary structuralelement of the prosthetic valve is facilitated, in accordance with thetechniques described herein.

For some applications of the invention, the implantation of implant 30follows an alternative order to that described with reference to FIGS.1A-H. For these applications of the invention, prosthetic valve 42 isinitially delivered to ventricle 28. Subsequently, prosthetic valvesupport 40 is deployed within atrium 26. In these applications of theinvention, following deployment and positioning of prosthetic valvesupport 40 against the annulus of native valve 23, prosthetic valve 42is moved atrially (i.e., proximally) into the respective lumens of thenative valve and prosthetic valve support 40, and is deployed, asdescribed hereinabove.

For some applications of the invention, valve-anchoring elements 64anchor prosthetic valve 42 to the native valve in a manner thatrestricts both proximal and distal movement of the prosthetic valve. Forsuch applications of the invention, deployment of prosthetic valve 42may occur in the reverse orientation, such that, following positioningin the native valve of prosthetic valve 42 compressed in delivery tube60, the delivery tube is moved distally (i.e., ventricularly) asprosthetic valve 42 is deployed from the delivery tube. Delivery tube 60is then removed from the subject via the lumen of the deployedprosthetic valve. It is hypothesized that this approach facilitatesmaneuvering of implant components and delivery apparatus, both fordelivery of implant 30 and for withdrawal of delivery apparatus. Forexample, this approach is hypothesized to require less space on theproximal side of the native valve (e.g., in the atrium), compared totechniques whereby the prosthetic valve is deployed from the proximalside of the native valve. An example of this approach is described withreference to FIGS. 15A-E.

For some applications of the invention, surfaces of one or morecomponents of implant 30 are covered at least in part with a covering(not shown). For example, surfaces of prosthetic valve support 40 andprosthetic valve 42 may be covered so as to direct substantially allblood flowing through the valve, to flow through the lumen of prostheticvalve 42. For some applications, the surface of prosthetic valve support40 (or another component) that is placed in contact with the nativevalve is covered; the covering is configured to facilitate coupling ofsupport 40 to the native valve, by enhancing fibrosis at the interfacebetween the prosthetic valve support and the native valve.

The covering may comprise polyethylene terephthalate (e.g., polyester),polytetrafluoroethylene (e.g., Teflon, ePTFE), or pericardial tissue.Typically, a thickness of the covering is less than 0.2 mm, e.g., lessthan 0.1 mm, or less than 0.05 mm.

For some applications, one or more dimensions of native valve 23 (e.g.,of leaflets 82, and/or of the annulus of the native valve) is measured(e.g., by using imaging techniques) prior to deployment of valve 42.Taking this measuring into account, a suitably-sized prosthetic valve ischosen to be placed in the annulus, in a manner in which across-sectional area of the prosthetic valve in its deployed state isless than 90% (e.g., less than 80%, or less than 60%) of the areadefined by the annulus.

For some applications, the cross-sectional area of the prosthetic valvein its deployed state has a longest length of less than 25 mm, e.g.,less than 20 mm, and/or more than 15 mm, e.g., 15-25 mm. For someapplications, placing a prosthetic valve inside the native valve, withthe dimensions of the native valve annulus and the prosthetic valve asdescribed, facilitates sealing of the prosthetic valve with respect tothe native valve, by the native valve leaflets closing around the outersurface of the prosthetic valve. In such applications, prosthetic valve42 is implanted directly within native valve 23 (i.e., without support40).

For some applications, prosthetic valve support 40, that is shaped todefine a lumen, is placed against the annulus of native valve 23 (e.g.,as described with reference to FIGS. 1A-H). The lumen of support 40 hasa cross-sectional area that is less than 90% (e.g., less than 80%, orless than 60%) of an area defined by native valve 23 (e.g., area A1,FIG. 71). As described hereinabove, prosthetic valve 42 is typicallycoupled to prosthetic valve support 40 and, thereby, to native valve 23,at least in part by expansion of the prosthetic valve such that primarystructural element 130 exerts a radial force against inner edge 68 ofprosthetic valve support 40. The cross-sectional area defined by theprimary structural element 130 of the prosthetic valve, upon expansionof the prosthetic valve, is limited by the cross-sectional area of thelumen of the prosthetic valve support 40 to less than 90% (e.g., lessthan 80%, or less than 60%) of the area defined by the annulus of thenative valve. For some applications, placing a prosthetic valve support40 at the native valve, as described, facilitates sealing of theprosthetic valve with respect to the native valve, by the native valveleaflets closing around the outer surface of the prosthetic valve.

Typically, placing a prosthetic valve inside the native valve with thedimensions of the native valve annulus, the prosthetic valve 42, and/orvalve support 40 as described in the above paragraphs, facilitatessealing of the prosthetic valve with respect to the native valve. Forsome applications, the sealing is facilitated by the native leafletsbeing pushed against, and closing against, the outer surface of theframe of the valve during systole, in a similar manner to the manner inwhich native valve leaflets coapt during systole, in a healthy mitralvalve.

Typically, as the diameter of the prosthetic valve is increased, theproportion of the native leaflets that is pushed against the outersurface of the valve during systole is increased, thereby enhancing thesealing of the native leaflets with respect to the frame of theprosthetic valve. However, beyond a given diameter, as the diameter ofthe prosthetic valve is increased, the native valve leaflets are pushedapart at the commissures, thereby causing retrograde leakage of bloodthrough the commissures. Therefore, in accordance with some applicationsof the present invention, prosthetic valve 42, and/or valve support 40are chosen such that the cross-sectional area of the prosthetic valve(when expanded inside the valve support) is less than 90% (e.g., lessthan 80%, or less than 60%) of the area defined by the annulus of nativevalve 23. Thus, the valve support facilitates additional sealing of theprosthetic valve with respect to the native valve, by the native valveleaflets closing around the outer surface of the prosthetic valve, whilenot causing retrograde leakage of blood through the commissures.

For some applications, in order to facilitate the sealing of the nativevalve around the outer surface of the prosthetic valve, a material isplaced on the outer surface of the prosthetic valve in order to providea sealing interface between the prosthetic valve and the native valve.For example, a smooth material that prevents tissue growth (e.g.,polytetrafluoroethylene (PTFE), and/or pericardium) may be placed on theouter surface of the prosthetic valve. Alternatively or additionally, amaterial that facilitates tissue growth (such as polyethyleneterephthalate; PET) may be placed on the outer surface of the prostheticvalve, in order to (a) act as a sealing interface between the nativevalve and the prosthetic valve, and (b) facilitate tissue growth aroundthe prosthetic valve to facilitate anchoring and/or sealing of theprosthetic valve.

For some applications, one or more dimensions of native valve 23 (e.g.,of leaflets 82, and/or of the annulus of the native valve) are measured(e.g., by using imaging techniques) prior to deployment of prostheticvalve 42 and/or prosthetic valve support 40. Taking this measuring intoaccount, a suitably-sized and/or suitably-configured prosthetic valveand/or prosthetic valve support is selected for implantation. Forexample, a prosthetic valve or prosthetic valve support comprisingtissue-engaging elements 62 with appropriate configurations and/ordimensions may be selected.

Reference is made to FIG. 2, which is a schematic illustration ofprosthetic valve support 40, comprising adjustable prosthetic valvesupport 40 e, which comprises tissue-engaging elements 62, comprisingsupport-anchoring elements 66 e, in accordance with some applications ofthe invention. Each support anchoring element 66 e comprises, or iscoupled to, a holding wire 522, which is slidably coupled to an upstreamsupport portion 41 (e.g., an annular portion) of support 40 e. Duringimplantation, support 40 e is anchored to native valve 23 viasupport-anchoring elements 66 e. For example, elements 66 e may engagecommissures 84 or leaflets 82 of the native valve, as describedhereinabove. The distance between upstream support portion 41 of support40 e and a coupling portion 70 of anchoring element 66 e, is adjustableby adjusting the length of the portion of holding wire 522 that couplesthe upstream support portion to the coupling portion. Some examples oftechniques for adjusting this length are described hereinbelow, withreference to FIGS. 3 and 4.

For some applications of the invention, at least part of holding wire522 is disposed in a connector 540, which further couples couplingportion 70 to upstream support portion 41. Holding wire 522 may beslidable through connector 540. For some applications, connector 540 ismore rigid than holding wire 522.

Reference is made to FIG. 3, which is a schematic illustration ofprosthetic valve support 40, comprising adjustable prosthetic valvesupport 40 f, which comprises tissue-engaging elements 62, comprisingsupport-anchoring elements 66 f, in accordance with some applications ofthe invention. Each support anchoring element 66 f comprises, or iscoupled to, a holding wire 522 f, which is slidably coupled to upstreamsupport portion 41 of support 40 f. During implantation, support 40 f isanchored to native valve 23 via support-anchoring elements 66 f. Forexample, elements 66 f may engage commissures 84 or leaflets 82 of thenative valve, as described herein. The distance between upstream supportportion 41 of support 40 f and a coupling portion of anchoring element66 f, is adjustable by adjusting the length of holding wire 522 f.Typically, holding wire 522 f is slidably coupled to upstream supportportion 41 of support 40 f via a ratchet 526, wherein holding wire 522 fis slidable through a ratchet housing 524, and comprises a plurality ofteeth 523 which allow the holding wire to slide through the ratchethousing in one direction, and restrict such sliding in anotherdirection. Such adjustment of holding wire 522 f may be performed whilesupport 40 f is partially deployed, or after the support has been fullydeployed.

FIG. 3 shows ratchet housing 524 being slidable over holding wire 522 f,such that the ratchet housing is movable with respect to upstreamsupport portion 41 of support 40 f. For this application of theinvention, a controller tube 528 is typically used to slide (e.g., push)ratchet housing 524 over holding wire 522 f, so as to adjust thedistance between upstream support portion 41 of support 40 f and thecoupling portion. For other applications of the invention, ratchethousing 524 is substantially stationary with respect to upstream supportportion 41 (e.g., ratchet housing 524 is attached to and/or embedded inportion 41), and holding wire 522 is slid (e.g., pulled) through housing524, so as to adjust the distance between upstream support portion 41 ofsupport 40 f and coupling portion 70.

As described with reference to FIG. 2, for some applications of theinvention, at least part of holding wire 522 (e.g., wire 5220 isdisposed in a connector 540 (e.g., connector 5401), which furthercouples coupling portion 70 to upstream support portion 41 of support 40f. Holding wire 522 f may be slidable through connector 540 f. Connector540 f is typically more rigid that holding wire 522 f:

It is hypothesized that adjusting the position of coupling portion 70 ofsupport-anchoring elements 66 f, with respect to upstream supportportion 41 of prosthetic valve support 40 f, allows prosthetic valvesupport 40 f to be adapted to the anatomy of the subject during and/orsubsequent to the implantation procedure.

Reference is made to FIG. 4, which is a schematic illustration ofprosthetic valve support 40, comprising adjustable prosthetic valvesupport 40 g, which comprises tissue-engaging elements 62, comprisingsupport-anchoring elements 66 g, in accordance with some applications ofthe invention. Each support anchoring element 66 g comprises, or iscoupled to, a holding wire 522, which is slidably coupled to upstreamsupport portion 41 of support 40 g. During implantation, support 40 g isanchored to native valve 23 via support-anchoring elements 66 g. Forexample, elements 66 g may engage commissures 84 or leaflets 82 of thenative valve, as described herein. The distance between upstream supportportion 41 of support 40 g and a coupling portion 70 (not shown) ofanchoring element 66 g, is adjustable by adjusting the length of holdingwire 522 g. Holding wire 522 g is coupled to a spool 460, such thatoperation (e.g., turning) of spool 460 withdraws and/or ejects portionsof the holding wire, thereby adjusting the length of holding wire 522 gthat couples the upstream support portion to the coupling portion,thereby adjusting the distance between upstream support portion 41 andcoupling portion 70. Such adjustment of holding wire 522 g may beperformed while support 40 g is partially deployed, or after the supporthas been fully deployed.

As described with reference to FIG. 2, for some applications of theinvention, at least part of holding wire 522 (e.g., wire 522 g) isdisposed in a connector 540 (e.g., connector 540), which further couplescoupling portion 70 to upstream support portion 41 of support 40 g.Holding wire 522 g may be slidable through connector 540 g. In someapplications, connector 540 g is more rigid that holding wire 522 g.

It is hypothesized that adjusting the position of coupling portion 70 ofsupport-anchoring elements 66 g, with respect to upstream supportportion 41 of prosthetic valve support 40 g, allows prosthetic valvesupport 40 g to be adapted to the anatomy of the subject during and/orsubsequent to the implantation procedure.

Reference is made to FIG. 5, which is a schematic illustration ofprosthetic valve support 40, comprising graduated prosthetic valvesupport 40 h, which comprises tissue-engaging elements 62, comprisingsupport-anchoring elements 66 h, in accordance with some applications ofthe invention. Each support-anchoring element 66 h is coupled toupstream support portion 41 of support 40 h via a graduated connector542. Graduated connector 542 comprises a plurality of coupling points543, to which coupling portion 70 of element 66 h is couplable. Prior toimplantation of prosthetic valve support 40 h, the distance betweenupstream support portion 41 of support 40 h and coupling portion 70 isadjustable, by selecting the coupling point 543 to which each couplingportion 70 is coupled.

It is hypothesized that adjusting the position of coupling portion 70 ofsupport-anchoring elements 66 h, with respect to upstream supportportion 41 of prosthetic valve support 40 h, allows prosthetic valvesupport 40 h to be adapted to the anatomy of the subject during and/orsubsequent to the implantation procedure.

Reference is made to FIG. 6, which is a schematic illustration ofprosthetic valve support 40, comprising flexibly-anchored prostheticvalve support 40 i, which comprises tissue-engaging elements 62,comprising support-anchoring elements 66 i, in accordance with someapplications of the invention. Each support-anchoring element 66 i iscoupled to upstream support portion 41 of support 40 i via a connector540, such as flexible connector 544. Flexible connector 544 typicallycomprises a flexible material which typically, but not necessarily,comprises polyethylene terephthalate (e.g., polyester),polytetrafluoroethylene (e.g., Teflon, ePTFE), silicone (e.g., siliconerubber), and/or or pericardial tissue. Flexible connector 544facilitates movement of coupling portion 70 of elements 66 i to movewith respect to upstream support portion 41 of support 40 i. It ishypothesized that this flexibility allows elements 66 i to anchorprosthetic valve support 40 i to the native valve (e.g., by coupling toleaflets 82), whilst allowing leaflets 82 to continue to function, atleast in part.

Reference is made to FIG. 7, which is a schematic illustration ofprosthetic valve support 40, comprising flexibly-anchored prostheticvalve support 40 j, which comprises tissue-engaging elements 62,comprising support-anchoring elements 66 j, in accordance with someapplications of the invention. Coupling portion 70 of each element 66 jis coupled to upstream support portion 41 of support 40 j via at leastone connector ring 548. Connector ring 548 typically facilitatesmovement of coupling portion 70 with respect to upstream support portion41. Each support-anchoring element 66 j typically comprises a connector540, such as flexible connector 546. Flexible connector 546 typicallycomprises a flexible material which typically, but not necessarily,comprises polyethylene terephthalate (e.g., polyester),polytetrafluoroethylene (e.g., Teflon, ePTFE), silicone (e.g., siliconerubber), and/or or pericardial tissue. Flexible connector 546 typicallyfurther facilitates coupling portion 70 to move with respect to upstreamsupport portion 41 of support 40 j. It is hypothesized that thisflexibility allows elements 66 j to anchor prosthetic valve support 40 jto the native valve (e.g., by coupling to leaflets 82), whilst allowingleaflets 82 to continue to function, at least in part.

Reference is made to FIGS. 8A-B, which are schematic illustrations ofprosthetic valve support 40, and prosthetic valve 42, the prostheticvalve comprising an integrally-anchoring prosthetic valve 42 a, whichcomprises support-engaging elements 422 comprising a plurality ofintegral support-engaging elements 424, in accordance with someapplications of the invention. For some applications of the invention,support-engaging elements 422 comprise other valve-anchoring elementsdescribed herein, such as valve-anchoring elements 64.

Reference is now made to FIG. 8A. Prosthetic valve 42 a comprises alattice structure, comprising a plurality of struts which typicallycollectively define a tessellation of shapes and voids. In some regionsof the prosthetic valve, there is a separation between adjacent shapes.This separation allows a portion of the shape to move or be moved out ofthe plane of the lattice, thereby protruding from primary structuralelement 130 of prosthetic valve 42 a when the prosthetic valve isexpanded. The protruding portion of the shapes thereby form integralsupport-engaging elements 424, which are typically configured to anchorprosthetic valve 42 a to the distal side of prosthetic valve support 40.

Reference is made to FIG. 8B, which shows implant 30, comprisingprosthetic valve 42 a and prosthetic valve support 40, implanted innative valve 23. FIG. 8B shows implant 30, comprising prosthetic valvesupport 40 and prosthetic valve 42 a, implanted in native valve 23,comprising mitral valve 24. Prosthetic valve support 40 typicallycomprises a plurality of tissue-engaging elements 62, comprisingsupport-anchoring elements 66, which engage leaflets 82 and/or chordaetendineae 80, and/or commissures 84, thereby anchoring support 40 to thenative valve. Prosthetic valve 42 a is compressible (e.g., crimpable)and expandable, and typically comprises a shape-memory material, asdescribed hereinabove with reference to prosthetic valve 42. Prostheticvalve 42 a is configured (e.g., shape-set) such that support-engagingelements 422, comprising integral support-engaging elements 424, arebiased to protrude from the surface of primary structural element 130.In this application of the present invention, primary structural element130 of prosthetic valve 42 a is generally cylindrical, and integralsupport-engaging elements 424 protrude radially from the surface of thecylinder. Because integral support-engaging elements 424 are formed fromthe regular repeating structure of the lattice that forms prostheticvalve 42 a, support-engaging elements 424 fit back into the plane ofstructural element 130 when valve 42 a is crimped into delivery tube 60,prior to and even during implantation. Integral support-engagingelements 424, thereby typically do not increase the length nor thetransverse cross-sectional longest dimension of the crimpedconfiguration of prosthetic valve 42, as compared to those of any otherprosthetic valves that do not comprise support-engaging elements 422, orthat comprise elements 422 at a proximal end thereof.

As described hereinabove, prosthetic valve 42 is deployed by distalmovement out of delivery tube 60. FIG. 8B shows prosthetic valve 42 a ina fully-deployed state, such that integral support-engaging elements 424have emerged from delivery tube 60, and have assumed an unconstrained,expanded, resting configuration in which the integral support-engagingelements 424 protrude radially from the surface of primary structuralelement 130 of the prosthetic valve. In an expanded state of at leastthe proximal portion of valve 42 a, as shown in FIG. 8B, integralsupport-engaging elements 424 typically protrude up to and including 110degrees (e.g., between 10 and 60 degrees, such as between 15 and 30degrees) from the surface of primary structural element 130, in aresting state of support-engaging elements 424. That is, in theprotruded state, the proximal portions of support-engaging elements 424are distanced further from structural element 130 than the distalportions of support-engaging elements 424 which function as the pivotjoints 74 between support-engaging elements 424 and structural element130, as shown in FIG. 8A.

In the expanded state of support-engaging elements 424, theradially-protruding proximal portions thereof typically define across-sectional area, the longest dimension of which is typically longerthan a transverse cross-sectional longest dimension of the lumen definedby prosthetic valve support 40. That is, in the expanded state,support-engaging elements 424 increase a longest transversecross-sectional length of prosthetic valve 42 a, such that the longesttransverse cross-sectional length is longer than a longest transversecross-sectional length of the lumen defined by prosthetic valve support40. Thereby, the radially-protruding support-engaging elements 424restrict proximal movement of prosthetic valve 42 a with respect toprosthetic valve support 40, thereby anchoring prosthetic valve 42 a tothe distal side of prosthetic valve support 40, and to native valve 23.

Reference is made to FIGS. 9A-E, which are schematic illustrations ofdelivery apparatus 438, used to deploy a medical device 150, inaccordance with some applications of the invention. Delivery apparatus438 comprises a delivery tube 154 and a pushing member 140. Pushingmember 140 comprises a support 142 and one or more coupling tabs 146,extending from the support. In the application of the invention shown inFIG. 9A, support 142 comprises a core 144, and coupling tabs 146 extendradially from the core.

In some applications of the invention, support 142 is shaped to define aplate 148 at the proximal end of support 142. The dimensions andrelative positions of support 142, tabs 146, and plate 148 may beadjusted for the specific medical device 150 to be deployed usingdelivery apparatus 438. Support 142 is shaped to define a plurality ofconduits 492 (e.g., holes). Delivery apparatus 438 further comprises oneor more control filaments, such as retrieval wires 490, slidablydisposed in conduits 492. Typically, conduits 492 provide communicationbetween a proximal side of support 142 and a circumference of thesupport, such that a proximal end of each retrieval wire 490 is disposedat a site proximal to delivery tube 154, and a distal end of each wireis reversibly coupled to medical device 150, retrieval wires 490extending through conduits 492.

For some applications of the invention, retrieval wires 490 are coupledto medical device 150 by being looped around parts of the medical device(e.g., looped around a strut of the lattice structure, as shown in FIG.9D), and are uncouplable from the medical device by being unlooped. Forsome applications of the invention, retrieval wires 490 are coupled tomedical device 150 via a lock, such as a lock comprising a plug disposedin a tubular member (e.g., as described with reference to FIGS. 45A-Cand/or 64A-C, mutatis mutandis). It is to be noted that the scope of thepresent application includes other techniques for coupling retrievalwires 490 to medical device 150, and decoupling the retrieval wires. Inthe application of the invention described with reference to FIGS. 9A-E,medical device 150 comprises prosthetic valve 42.

FIG. 9B shows prosthetic valve 42 in a compressed (i.e., crimped)configuration for delivery and deployment using delivery apparatus 438.Prosthetic valve 42 typically has a lattice structure that defines aplurality of shapes, and respective voids 126 (FIG. 9C), and has shapememory (described in more detail hereinbelow, such as with reference toFIGS. 53A-C and 62A-D, mutatis mutandis). Prosthetic valve 42 is shownin a compressed (e.g., crimped) configuration, and as shown in theenlarged image, a proximal portion of valve 42 is disposed around (e.g.,against) core 144 of pushing member 140 such that each of coupling tabs146 is disposed within a respective void 126 defined by the latticestructure of the prosthetic valve.

Prosthetic valve 42 and pushing member 140 are disposed within the lumenof delivery tube 154. Delivery tube 154 restricts expansion ofprosthetic valve 42, thereby holding the proximal portion of prostheticvalve 42 around core 144 of pushing member 140, in the configurationdescribed herein. Coupling tabs 146 restrict movement of prostheticvalve 42 with respect to pushing member 140. Delivery tube 154 thereforefacilitates coupling of prosthetic valve 42 to pushing member 140 viacoupling tabs 146. In applications of the invention where pushing member140 is shaped to define plate 148, the plate typically furtherfacilitates this coupling by restricting proximal movement of prostheticvalve 42 with respect to the pushing member (i.e., by functioning as acap). Thereby, in the compressed configuration thereof, prosthetic valve42 is configured to be fixedly coupled to pushing member 140.

A control tube 152 is typically coupled at a distal end thereof topushing member 140 (e.g., control tube 152 is coupled to support 142).Control tube 152 is shaped so as to define a lumen through which aguidewire tube 153 passes, and control tube 152 is slidable with respectto and along guidewire tube 153. Guidewire tube 153 houses guidewire 45described hereinabove. Control tube 152 is slidably disposed within alumen of an overtube 155.

FIG. 9C shows prosthetic valve 42 partially deployed from delivery tube154. Pushing member 140, and, thereby, prosthetic valve 42, are moveddistally through delivery tube 154.

Reference is again made to FIG. 9C. Pushing member 140 is pusheddistally by pushing control tube 152 along guidewire tube 153 such thatpushing member 140 pushes prosthetic valve 42. As pushing member 140pushes valve 42 distally, distal portions of the prosthetic valve expandtoward the expanded configuration as they become exposed from deliverytube 154, while the proximal end of valve 42 remains coupled to pushingmember 140 via tabs 146.

FIG. 9D shows prosthetic valve 42 having been fully deployed from withindelivery tube 154. Pushing member 140 and prosthetic valve 42 are movedfurther distally through delivery tube 154 by control tube 152. When theproximal portion of prosthetic valve 42 emerges from within deliverytube 154, expansion of the proximal portion of prosthetic valve 42uncouples the prosthetic valve from coupling tabs 146 by expanding voids126 away from tabs 146, thereby releasing the prosthetic valve frompushing member 140. For some applications, retrieval wires 490 aregenerally loose, such that expansion of prosthetic valve 42 pulls thewires through conduits 492, and radially outward from core 144. For someapplications, retrieval wires 490 are under tension, and are releasedgradually, so as to control expansion of prosthetic valve 42. That is,for some applications, the expansion of prosthetic valve 42 isrestricted (e.g., controlled) by the distal advancement of retrievalwires 490.

Should it be necessary and/or desirable during deployment, until medicaldevice 150 (e.g., prosthetic valve 42) is released from pushing member140 (i.e., while the proximal portion of medical device 150 is crimpedwithin delivery tube 154), the deployed, expanded portions of medicaldevice 150 (i.e., the portions of medical device 150 that are exposedfrom delivery tube 154) may be drawn back into delivery tube 154 (e.g.,for repositioning or withdrawal of the medical device).

Subsequent to deployment of prosthetic valve 42, should it be necessaryand/or desirable, the prosthetic valve may be drawn back against support142 (e.g., radially inward) by proximally pulling retrieval wires 490.Subsequently, prosthetic valve 42 may be drawn back, along with pushingmember 140, into delivery tube 154. That is, for some applications,prosthetic valve 42 is recompressible (i.e., the expansion of prostheticvalve 42 is at least in part reversible) by proximal retraction ofretrieval wires 490.

FIG. 9E shows retrieval wires 490 having been pulled proximally (e.g.,by a user), such that wires 490 pull at least part of prosthetic valve42 into a compressed configuration around and against support 142.Prosthetic valve 42 is thereby recoupled to pushing member 140. Pushingmember 140 and prosthetic valve 42 are moved proximally and drawn intodelivery tube 154. Prosthetic valve 42 may subsequently redeployed, orremoved from the subject along with delivery tube 154.

That is, (1) retrieval wires 490 are slidable through conduits 492 ofcore 144, and reversibly couplable to prosthetic valve 42, and (2)delivery apparatus 438 is configured to control and/or facilitate (a)expansion of prosthetic valve 42, by the retrieval wires being advanceddistally through the conduits, and (b) recompression of prosthetic valve42, by the retrieval wires being retracted proximally through theconduits.

Reference is now made to FIGS. 9A-E and 1D-F. It is to be noted thatdelivery tube 154 of FIGS. 9A-E is similar to, and/or may comprise,delivery tube 60 of FIGS. 1D-F.

Reference is made to FIG. 10, which is a schematic illustration ofprosthetic valve support 40, comprising multi-lumen prosthetic valvesupport 40 a, in accordance with some applications of the invention. Asdescribed hereinabove, prosthetic valve support 40 is generally annularand shaped to define a lumen, in which prosthetic valve 42 is deployedand expanded. In the application of the invention illustrated in FIG.10, prosthetic valve support 40, comprising multi-lumen prosthetic valvesupport 40 a, is shaped to define two or more lumens. That is, the wireframe of support 40 a defines two or more lumens. Prosthetic valvesupport 40 a is typically couplable to the native valve using techniquesdescribed herein for coupling other prosthetic valve supports to thenative valve. For example, prosthetic valve support 40 a may comprisetissue-engaging elements (e.g., support-anchoring elements). Similarly,other prosthetic valve supports described herein may comprise prostheticvalve support 40 a.

Prosthetic valve support 40 a is typically covered with a covering 440,such as a fabric. Covering 440 may comprise polyethylene terephthalate(e.g., polyester), polytetrafluoroethylene (e.g., Teflon, ePTFE), orpericardial tissue. Typically, a thickness of covering 440 is less than0.2 mm, e.g., less than 0.1 mm, or less than 0.05 mm. When support 40 ais supplied and/or implanted, covering 440 typically covers support 40 asuch that only a first lumen 444 is open and configured to receive aprosthetic valve, and the second lumen 446 is closed. That is, the wireframe of support 40 a defines two or more lumens but the coveringdefines only one lumen, thereby covering 440 functions as a seal 442.

In some applications of the invention, covering 440 is not disposed oversecond lumen 446; rather a different element functions as seal 442. Forexample, a weaker and/or softer material (e.g., pericardial tissue) or aremovable plug may be coupled to prosthetic valve support 40 a, anddisposed over second lumen 446 to function as seal 442.

Implant 30, comprising prosthetic valve 42 and prosthetic valve support40 a, is implanted in native valve 23 (e.g., as described with referenceto FIGS. 1A-H, mutatis mutandis), whereby prosthetic valve prostheticvalve 42 is deployed in first lumen 444 of the support. At a later time,a second prosthetic valve may be introduced by deploying the secondprosthetic valve in second lumen 446. That is, at a first period,prosthetic valve support 40 a facilitates implantation of a firstprosthetic valve at the native valve, and at a second period, theprosthetic valve support facilitates implantation of a second prostheticvalve at the native valve. In some applications of the invention, seal442 is opened, and thereby configured to receive a prosthetic valve(e.g., by being broken, cut and/or torn) by the introduction of thesecond prosthetic valve. In other applications, seal 442 is opened witha cutting tool (not shown) prior to deployment of the second prostheticvalve. In some applications of the invention, seal 442 is uncoupled fromsupport 40 a, prior to deployment of the second prosthetic valve.

For some applications of the invention, following the deployment of thesecond prosthetic valve, the first prosthetic valve (i.e., prostheticvalve 42) is disabled (e.g., sealed). For example, an expandable plugmay be expanded in the lumen of the first prosthetic valve.

Prosthetic cardiac valves typically require replacement after severalyears (e.g., after 2-20 years, such as after 5-10 years). For example,the condition of the subject may change and/or components of theprosthetic valve (e.g., prosthetic valve leaflets) may suffer fatigue.It is hypothesized that multi-lumen prosthetic valve support 40 a allowsa second prosthetic valve to be implanted in the native valve, thesecond prosthetic valve being supported by the originally-implantedprosthetic valve support 40 a. The first prosthetic valve may be sealed,for example, if the original prosthetic valve allows, or is predicted toallow, retrograde leakage. Implantation of a second prosthetic valve ishypothesized to increase the lifespan of implant 30.

Reference is made to FIG. 11, which is a schematic illustration ofprosthetic valve support 40, comprising extended-lumen prosthetic valvesupport 40 e, in accordance with some applications of the invention. Asdescribed hereinabove, prosthetic valve support 40 is generally annularand shaped to define a lumen, in which prosthetic valve 42 is deployedand expanded. Extended-lumen prosthetic valve support 40 e is shaped todefine a lumen 448, which has an extended dimension. That is, the wireframe of support 40 e typically defines lumen 448, which has (1) aprimary region 447, and (2) a secondary region 449 that is generally notfilled by expansion of prosthetic valve 42 in the lumen. Typically,lumen 448 has a first length that is longer than, and generallyorthogonal to, a second length, and has one or more concave portions.For example, lumen 448 may be generally shaped to define an oval orellipse with one or more concave portions generally midway along thefirst length (e.g., a Cassini oval or a hippopede). Prosthetic valvesupport 40 e is typically couplable to the native valve using techniquesdescribed herein for coupling other prosthetic valve supports to thenative valve. For example, prosthetic valve support 40 e may comprisetissue-engaging elements (e.g., support-anchoring elements). Similarly,other prosthetic valve supports described herein may comprise prostheticvalve support 40 e.

Prosthetic valve support 40 e is typically covered with a covering 440,such as a fabric. Covering 440 may comprise polyethylene terephthalate(e.g., polyester), polytetrafluoroethylene (e.g., Teflon, ePTFE), orpericardial tissue. Typically, a thickness of covering 440 is less than0.2 mm, e.g., less than 0.1 mm, or less than 0.05 mm. When support 40 eis supplied and/or implanted, covering 440 typically covers support 40 esuch that secondary region 449 is closed. That is, the wire frame ofsupport 40 e defines a generally elongated lumen 448, whilst covering440 defines a generally round primary region 447. In this manner,covering 440 functions as a seal 442 over secondary region 449.

In some applications of the invention, covering 440 is not disposed oversecondary region 449; rather a different element functions as seal 442.For example, a weaker and/or softer material (e.g., pericardial tissue)or a removable plug may be coupled to prosthetic valve support 40 e, anddisposed over secondary region 449, so as to function as seal 442.

Implant 30, comprising prosthetic valve 42 and prosthetic valve support40 e, is implanted in native valve 23 (e.g., as described with referenceto FIGS. 1A-H), whereby prosthetic valve 42 is deployed in primaryregion 447 of the support. At a later time, a second prosthetic valvemay be introduced by deploying the second prosthetic valve in secondaryregion 449. That is, at a first period, prosthetic valve support 40 efacilitates implantation of a first prosthetic valve at the nativevalve, and at a second period, the prosthetic valve support facilitatesimplantation of a second prosthetic valve at the native valve. In someapplications of the invention, seal 442 is opened (e.g., broken, cutand/or torn) by the introduction of the second prosthetic valve. Inother applications, seal 442 is opened with a cutting tool (not shown)prior to deployment of the second prosthetic valve. In some applicationsof the invention, seal 442 is uncoupled from support 40 e, prior todeployment of the second prosthetic valve.

Typically, expansion of the second prosthetic valve during deploymentdeforms the first prosthetic valve (i.e., a radially-expansive force ofthe second prosthetic valve is stronger than that of the firstprosthetic valve). For example, following deployment of the secondvalve, the first valve may assume a lune shape or a generallysemicircular shape. In some applications of the invention, the secondprosthetic valve is shaped to fit into secondary region 449 withoutdeforming the first prosthetic valve.

Prosthetic cardiac valves typically require replacement after severalyears (e.g., after 2-20 years, such as after 5-10 years). For example,the condition of the subject may change and/or components of theprosthetic valve (e.g., prosthetic valve leaflets) may suffer fatigue.It is hypothesized that extended-lumen prosthetic valve support 40allows a second prosthetic valve to be implanted in the native valve,the second prosthetic valve being supported by the originally-implantedprosthetic valve support 40. The first prosthetic valve may be sealed,as described hereinabove, for example, if the original prosthetic valveallows, or is predicted to allow, retrograde leakage. Implantation of asecond prosthetic valve is hypothesized to increase the lifespan ofimplant 30.

Reference is made to FIGS. 12A-B, which are schematic illustrations ofprosthetic valve support 40, comprising adjustable-lumen prostheticvalve support 40 b, in accordance with some applications of theinvention. As described hereinabove, expansion of prosthetic valve 42 isrestricted by the lumen of prosthetic valve support 40. As furtherdescribed hereinabove, the optimum lumen size may depend on theindividual subject and/or condition being treated. Adjusting the size ofthe lumen of prosthetic valve 42 is hypothesized to alter the flow ofblood through the prosthetic valve, and the sealing of leaflets 82 ofthe native valve against the outer surface of the prosthetic valve. Insome applications of the invention, the size of the area defined by theannulus of the native valve is measured (e.g., using a measuring ringand/or using imaging techniques), and appropriately-sized prostheticvalve 42 and prosthetic valve support 40 are selected for implantation.FIGS. 12A-B show adjustable-lumen prosthetic valve support 40 b, whichcomprises a spool 461 and a tightening wire 462. Tightening wire 462typically forms a loop around a central portion of support 40 b (e.g.,threadedly coupled around an inner edge 68), and is coupled to spool 461such that the tightening wire can be tightened (i.e., shortened) viaspool 461. FIG. 12A shows support 40 b with a larger lumen (i.e., whentightening wire 462 is relatively loose) and FIG. 12B shows support 40 bwith a smaller lumen, following tightening of tightening wire 462 with atightening tool 464.

For some applications, prosthetic valve support 40 b and prostheticvalve 42 are implanted as described herein (e.g., with reference toFIGS. 1A-H), and tightening wire 462 is subsequently tightened. For someapplications, the annulus of the native valve is measured, andtightening wire 462 is responsively adjusted, prior to implantation. Forsome applications, following measurement of the native valve, and priorto implantation, a support 40 b of appropriate size is selected from arange.

Reference is made to FIGS. 13A-D, which are schematic illustrations ofprosthetic valve support 40, comprising asymmetric prosthetic valvesupport 40 c, in accordance with an application of the invention. Asdescribed hereinabove, support 40 is generally annular, and shaped todefine a lumen. FIG. 13A shows that the lumen defined by support 40 c(i.e., oblique lumen 480) is typically not central with respect to thesupport. That is, support 40 c is typically rotationally asymmetric.Support 40 c typically defines a total cross-sectional area of between16 cm{circumflex over ( )}2 and 38 cm{circumflex over ( )}2 (e.g.,between 22 cm{circumflex over ( )}2 and 28 cm{circumflex over ( )}2).Typically, the cross-sectional area of lumen 480 is less than 70% (e.g.,less than 60%, or less than 40%) of the cross-sectional area of area ofsupport 40 c. For example, for some applications, the cross-sectionalarea of lumen 480 has a longest length of less than 25 mm, e.g., lessthan 20 mm, and/or more than 15 mm, e.g., 15-25 mm. As describedhereinabove, for some applications, surfaces of prosthetic valve support40 are covered with a covering so as to direct substantially all bloodto flow through the lumen of prosthetic valve 42. Asymmetric prostheticvalve support 40 c is typically not covered, i.e., the lattice structureof which the support is comprised, is exposed.

FIG. 13B shows prosthetic valve support 40 c having been deployed to theannulus of native valve 23, as described herein (e.g., with reference toFIGS. 1A-H). For the applications of the invention described withreference to FIGS. 13A-D, prosthetic valve support typically comprises aplurality of tissue-engaging elements (e.g., support-anchoringelements), such as those described herein (not shown in FIGS. 13A-D).Support-anchoring elements 66 are typically configured and oriented toengage commissures 84 of the native valve, so as to anchor support 40 tothe native valve whilst allowing leaflets 82 to continue to function.Prosthetic valve support 40 c is typically deployed to native valve 23such that lumen 480 is positioned over (i.e., proximal to) a place ofcoaptation of the two leaflets 82 of the native valve. Subsequently,prosthetic valve 42 is deployed in lumen 480 (as described hereinabove;e.g., with reference to FIGS. 1A-H), such that, in the expanded state,prosthetic valve 42 is disposed between leaflets 82.

FIG. 13C shows implant 30, comprising prosthetic valve support 40 c andprosthetic valve 42, implanted in native valve 23, in accordance with anapplication of the invention. Typically, but not necessarily, prostheticvalve 42 does not comprise valve-anchoring elements 64. Rather,prosthetic valve 42 is typically anchored to native valve 23 by beingcoupled to support 40 c, which is, itself, anchored to the native valve,as described hereinabove. Prosthetic valve 42 is positioned betweenleaflets 82 of the native valve, due to the oblique position of lumen480 of support 40 c. Typically, leaflets 82 are generally free to movewith respect to the prosthetic valve, and move proximally and distallywith the beating of the heart, coapting and sealing around prostheticvalve 42. This movement of leaflets 82 is facilitated by support 40 cbeing uncovered and fluid communication being maintained between atrium26 and ventricle 28 through the lattice structure of support 40 c. Forexample, when native valve 23 comprises mitral valve 24, duringdiastole, leaflets 82 open, and left atrial blood moves into the leftventricle, both through and around prosthetic valve 42 (i.e., throughthe lumen of prosthetic valve 42 and through the exposed latticestructure of support 40 c). During systole, leaflets 82 close, i.e.,coapt together, and seal around prosthetic valve 42, restrictingretrograde movement of blood.

It is hypothesized that over a period of time (e.g., a week, e.g., amonth, e.g., a year) following implantation of implant 30 comprisingsupport 40 c, movement of leaflets 82 is reduced (e.g., due to tissuegrowth and/or calciferous deposits), such that the functionality ofnative valve 23 is gradually reduced, and the proportion of blood thatflow through prosthetic valve 42, relative to that which flows aroundthe prosthetic valve, is increased. That is, over time, prosthetic valve42 takes over the function of native valve 23.

Reference is made to FIG. 14, which is a schematic illustration ofprosthetic valve support 40, comprising prosthetic valve support 40 d,which comprises tissue-engaging elements 62, comprising a plurality ofsupport-anchoring elements 66 a, in accordance with some applications ofthe invention. Typically, support 40 d comprises two elements 66 a,typically coupled to inner edge 68, and positioned generally oppositeeach other. Elements 66 a typically comprise two or more (e.g., three)coupling portions 70, which extend radially from a structural component71. FIG. 14 shows elements 66 a comprising three coupling portions 70,arranged in a T-shape. Support 40 d is typically deployed in the nativevalve such that elements 66 a are oriented toward commissures 84 of thenative valve, and engage both the commissures and the closest regions ofleaflets 82. It is hypothesized that this structure and positioning ofelements 66 a anchor support 40 d to the native valve, whilst allowingleaflets 82 to move, thereby allowing native valve 23 to continue tofunction, at least partly, until prosthetic valve 42 is deployed.

Reference is made to FIGS. 15A-E, which are schematic illustrations ofthe implantation of prosthetic valve support 40 and prosthetic valve 42,in accordance with some applications of the invention. Prosthetic valve42 is compressible (e.g., crimpable) and expandable, and typicallycomprises a shape-memory material, as described hereinabove. FIG. 15Ashows prosthetic valve support 40 having been deployed to the annulus ofnative valve 23, and prosthetic valve 42 having been delivered, in thecrimped configuration thereof, within delivery tube 60 a, to the nativevalve. Prosthetic valve 42 and delivery tube 60 a are disposed in thelumen of native valve 23. Leaflets 82 of the native valve typicallycoapt and seal around delivery tube 60 a. The proximal end of deliverytube 60 a is shown open.

FIG. 15B shows delivery tube 60 a being moved distally while prostheticvalve 42 remains relatively stationary, thereby exposing the prostheticvalve from the delivery tube. As portions of prosthetic valve 42 areexposed, they expand from the crimped configuration to an expandedconfiguration. Typically, expansion of the proximal portion ofprosthetic valve 42 facilitates coupling of the prosthetic valve toprosthetic valve support 40. In the application of the inventionillustrated by FIGS. 15A-E, prosthetic valve 42 is shaped to define awidened proximal end, which facilitates coupling of prosthetic valve 42to prosthetic valve support 40. It is to be noted that the scope of thepresent application includes other configurations of prosthetic valve42, such as those included herein.

FIG. 15C shows delivery tube 60 a having been removed entirely fromprosthetic valve 42, and prosthetic valve 42 having expanded to itsexpanded configuration, the expansion facilitating coupling of theprosthetic valve to support 40 and, thereby, native valve 23. Deliverytube 60 a is shown in left ventricle 28 of the heart.

FIGS. 15D and 15E show delivery tube 60 a being withdrawn proximally,through the lumen of prosthetic valve 42. Delivery tube 60 a issubsequently removed from the subject. Typically, delivery tube 60 a iswithdrawn between leaflets of prosthetic valve 42 (not shown), which aretypically disposed in the lumen of the prosthetic valve. Typically,delivery tube 60 a is withdrawn into overtube 44 prior to removal fromthe subject. It is to be noted that the scope of the present applicationincludes deployment of the prosthetic valve from the distal (i.e.,ventricular) side of native valve 23, and the withdrawal of the deliverytube via the lumen of the prosthetic valve. It is hypothesized that thisapproach facilitates maneuvering of implant components and deliveryapparatus, both for delivery of implant 30 and for withdrawal ofdelivery apparatus. For example, this approach is hypothesized torequire less space on the proximal side of the native valve (e.g., inatrium 26), compared to techniques whereby the prosthetic valve isdeployed from the proximal side of the native valve.

Reference is made to FIG. 16, which is a schematic illustration ofprosthetic valve support 40 being deployed in native valve 23,comprising mitral valve 24, in accordance with some applications of theinvention. Support 40 is typically delivered to the native valve in acompressed (e.g., crimped) configuration, within overtube 44. In thecompressed configuration, support 40 typically assumes a tubular shape,having a proximal end and a distal end. Typically, the distal end isdefined by inner edge 68 (described hereinabove), and tissue-engagingelements 62, comprising support-anchoring elements 66, extend distallyfrom the distal end. To deploy support 40, the support is moved (e.g.,pushed) through overtube 44, such that support-anchoring elements 66emerge from the overtube. Support-anchoring elements 66 engage nativevalve 23, typically by grasping leaflets 82, commissures 84, and/orchordae tendineae 80 of the native valve. Subsequently, the remainingportions of support 40 (e.g., upstream support portion 41) are moved outof overtube 44, and support 40 expands to assume its expanded, generallyannular, shape. Prosthetic valve support 40 is thereby anchored to thenative valve, typically with upstream support portion 41 held againstthe annulus of the native valve, by support-anchoring elements 66 (e.g.,as described hereinabove).

In some applications of the invention, support-anchoring elements 66 areconfigured and/or arranged so as to anchor prosthetic valve support 40to the native valve (e.g., by engaging leaflets 82, and/or commissures84, and/or chordae tendineae 80), whilst allowing leaflets 82 tocontinue to function, at least in part.

In some applications of the invention, should it be necessary and/ordesirable, support 40 is retrievable before it is fully deployed, bywithdrawing the support proximally, back into overtube 44.

In some applications, should it be necessary and/or desirable, support40 is retrievable after it has been fully deployed. For example, support40 may be drawn back around and against a pushing member of deliveryapparatus, recompressing support 40 for withdrawal into a delivery tube,in a similar way to the technique described with reference to FIGS.9A-E, mutatis mutandis. Prosthetic valve support 40 may subsequently beremoved from the subject, and/or repositioned, and/or redeployed.

Reference is made to FIGS. 17A-D, which are schematic illustrations ofsupport 40, comprising tissue-engaging elements 62, which comprisesupport-anchoring elements 66, comprising length-adjustable holdingelements 600, in accordance with some applications of the invention.Native heart valves vary naturally in various dimensions, such as, butnot limited to, the length, width and/or thickness of leaflets 82, thedistance between commissures 84, and/or the distance between fibroustrigones. In this context, in the specification and in the claims, thesevarying parameters are referred to as “dimensions.” Length-adjustableholding elements 600 are configured such that the distance betweencoupling portion 70 and upstream support portion 41 of prosthetic valvesupport 40 is adjustable. This adjustability typically facilitatesplacement (i.e., implantation) of the prosthetic valve support at nativevalves of different dimensions, such that (1) upstream support portion41 is placeable against the proximal (i.e., atrial) side of theprosthetic valve, and (2) coupling portion 70 is placeable on the distal(i.e., ventricular) side of the native valve (e.g., to engage the nativeleaflets and/or commissures, as described hereinabove).

For some applications, coupling portions 70 engage (e.g., are coupledto) leaflets 82 and/or commissures 84 of native valve 23 whileprosthetic valve support 40 is still in a partially-deployedconfiguration (e.g., as described with reference to FIGS. 1B and 16).For some applications, support 40 is first expanded, upstream supportportion 41 is then placed against the annulus of the native valve, andcoupling portions 70 subsequently engage (e.g., are coupled to) theleaflets and/or commissures.

In the applications of the invention described with reference to FIGS.17A-D, holding elements 600 are typically biased to assume a contractedconfiguration, and are typically expanded (e.g., stretched) so as tocouple portions 70 to the native valve. This bias thereby provides apulling force, which is hypothesized to facilitate coupling ofprosthetic valve support 40 to native valve 23 by sandwiching the nativevalve between upstream support portion 41 and coupling portion 70, insome applications of the invention.

Typically, adjustment and/or other manipulation of support-anchoringelements 66, comprising length-adjustable holding elements 600, may beperformed prior to the implantation procedure, e.g., followingimaging-based sizing of one or more dimensions of native valve 23 (e.g.,of leaflets 82, and/or of the annulus of the native valve), and/orduring the implantation procedure (e.g., when the prosthetic valvesupport is at the site of implantation).

FIG. 17A shows prosthetic valve support 40, comprising prosthetic valvesupport 40 n, which comprises support-anchoring elements 66, comprisingsupport-anchoring elements 66 n. Each support-anchoring element 66 ncomprises a coupling portion 70, coupled to upstream support portion 41of support 40 n via a length-adjustable holding element 600, comprisinga stretchable holding element 600 n. Stretchable holding element 600 ncomprises a tension spring, typically comprising a coil spring.Stretchable holding element 600 n facilitates adjusting the distancebetween coupling portion 70 and upstream support portion 41 such that,for native valves of different dimensions, (1) upstream support portion41 is placeable against the proximal (i.e., atrial) side of theprosthetic valve, and (2) coupling portion 70 is placeable on the distal(i.e., ventricular) side of the native valve (e.g., to engage the nativeleaflets and/or commissures, as described hereinabove).

FIG. 17B shows prosthetic valve support 40, comprising prosthetic valvesupport 40 p, which comprises support-anchoring elements 66, comprisingsupport-anchoring elements 66 p. Each support-anchoring element 66 pcomprises a coupling portion 70, coupled to upstream support portion 41of support 40 p via length-adjustable holding element 600, comprising astretchable holding element 600 p. Stretchable holding element 600 pcomprises a tension spring, typically comprising a zigzag-shaped pieceof material, such as a shape-memory material, e.g., nitinol. Stretchableholding element 600 p facilitates adjusting the distance betweencoupling portion 70 and upstream support portion 41 such that, fornative valves of different dimensions, (1) upstream support portion 41is placeable against the proximal (i.e., atrial) side of the prostheticvalve, and (2) coupling portion 70 is placeable on the distal (i.e.,ventricular) side of the native valve (e.g., to engage the nativeleaflets and/or commissures, as described hereinabove).

FIG. 17C shows prosthetic valve support 40, comprising prosthetic valvesupport 40 q, which comprises support-anchoring elements 66, comprisingsupport-anchoring elements 66 q. Each support-anchoring element 66 qcomprises a coupling portion 70, coupled to upstream support portion 41of support 40 q via length-adjustable holding element 600, comprising astretchable holding element 600 q. Stretchable holding element 600 qcomprises a tension spring, typically comprising an elastic tube 602,such as a tube of elastic silicone. Stretchable holding element 600 qfacilitates adjusting the distance between coupling portion 70 andupstream support portion 41 such that, for native valves of differentdimensions, (1) upstream support portion 41 is placeable against theproximal (i.e., atrial) side of the prosthetic valve, and (2) couplingportion 70 is placeable on the distal (i.e., ventricular) side of thenative valve (e.g., to engage the native leaflets and/or commissures, asdescribed hereinabove).

For some applications of the invention, stretchable holding element 600q further comprises a limiting wire 604, typically coupled to upstreamsupport portion 41 and coupling portion 70. Limiting wire 604 isgenerally non-elastic, and is configured to limit the expansion (i.e.,stretching) of holding element 600 q. For example, limiting wire may beconfigured to prevent overstretching of holding element 600 q, e.g., toprevent failure of the holding element. Typically, limiting wire 604 islonger than the length of elastic tube 602 in the relaxed (i.e.,contracted) configuration thereof, and is shorter than the length ofelastic tube 602 in a maximally-expanded (i.e., maximally-stretched)configuration thereof. In the relaxed (i.e., contracted) configurationof elastic tube 602, limiting wire 604 is typically loose (e.g.,generally bent, crumpled, flexed). When elastic tube 602 is expanded(i.e., stretched), limiting wire 604 typically becomes taut (e.g.,generally straight), thereby limiting the expansion of elastic tube 602to generally the length of limiting wire 604.

It is to be noted that the scope of the present invention includes theuse of limiting wire 604 in combination with other length-adjustableholding elements including, but not limited to, stretchable holdingelement 600 n, described with reference to FIG. 17A.

FIG. 17D shows prosthetic valve support 40, comprising prosthetic valvesupport 40 u, which comprises support-anchoring elements 66, comprisingsupport-anchoring elements 66 u. Each support-anchoring element 66 ucomprises a coupling portion 70, coupled to upstream support portion 41of support 40 u via a length-adjustable holding element 600, comprisinga stretchable holding element 600 u. Stretchable holding element 600 ufacilitates adjusting the distance between coupling portion 70 andupstream support portion 41 such that, for native valves of differentdimensions, (1) upstream support portion 41 is placeable against theproximal (i.e., atrial) side of the prosthetic valve, and (2) couplingportion 70 is placeable on the distal (i.e., ventricular) side of thenative valve (e.g., to engage the native leaflets and/or commissures, asdescribed hereinabove). Stretchable holding element 600 u comprises atension spring, typically comprising a coil spring 610. For someapplications of the invention, coil spring 610 is generally similar tothe coil spring of stretchable holding element 600 n, as describedhereinabove. Stretchable holding element 600 u further comprises, or iscoupled to, a restrictor 612. Restrictor 612 typically holds spring 610in an expanded (i.e., stretched) configuration. Typically, restrictor612 is decouplable from spring 610. For some applications, restrictor612 may be mechanically removed by the user. For some applications,restrictor 612 may comprise a material that disintegrates in the body(e.g., a material that is at least in part soluble and/or biodegradableand/or bioresorbable). For these applications, restrictor 612 typicallydisintegrates over a predictable period of time e.g., between 15 minutesand 1 week, such as between 30 minutes and 3 days, for example, between1 h and 1 day. For some applications, restrictor 612 is configured todecouple from (i.e., release) spring 610 gradually, e.g., in stages. Forsome applications, restrictor 612 is coupled to spring 610 and/oranother part of prosthetic valve support 40 u, such that, following therelease of spring 610, the restrictor is retained so as not to enter thevasculature of the subject.

When spring 610 is released from restrictor 612, the spring relaxes(i.e., contracts), and provides a pulling force that sandwiches thenative valve between support 40 u and coupling portion 70, e.g., asdescribed hereinabove, mutatis mutandis.

Reference is made to FIGS. 18A-B, which are schematic illustrations ofprosthetic valve support 40, which comprises support-anchoring elements66, comprising length-adjustable holding elements 600, in accordancewith some applications of the invention.

FIG. 18A shows prosthetic valve support 40, comprising prosthetic valvesupport 40 r, which comprises support-anchoring elements 66, comprisingsupport-anchoring elements 66 r. Each support-anchoring element 66 rcomprises a coupling portion 70, coupled to upstream support portion 41of support 40 r via length-adjustable holding element 600, comprising atelescopic holding element 600 r. Telescopic holding element 600 rcomprises a plurality of portions, typically cylinders, which areslidable over and/or through each other. FIG. 18A shows telescopicholding element 600 r comprising two externally-threaded cylindersconnected by an internally-threaded cylinder, and configured such thatrotation of the internally-threaded cylinder with respect to theexternally-threaded cylinders adjusts the distance between theexternally-threaded cylinders. Thereby, rotation of theinternally-threaded cylinder adjusts the distance between couplingportion 70 and upstream support portion 41. Adjustment of this distancemay be performed prior to implantation of prosthetic valve support 40 r,and/or during the implantation procedure (e.g., after deployment ofsupport 40 r).

Reference is again made to FIGS. 17A-D, and 18A-B. The applications ofthe invention described with reference to FIGS. 17A-D, comprisesupport-anchoring elements 66 that comprise length-adjustable holdingelements 600, such as stretchable holding elements 600 n, 600 p, and 600q. In addition to being axially stretchable, these holding elements aretypically laterally flexible. This flexibility is hypothesized to beadvantageous in some applications of the invention. For example, in someapplications, leaflets 82 of the native valve may continue to function,at least in part, after support-anchoring elements 66 are coupled to theleaflets. In contrast, the adjustable holding elements 600 describedwith reference to FIGS. 18A-B (i.e., elements 600 r and 600 t) aretypically laterally rigid.

Reference is again made to FIG. 18B, which shows prosthetic valvesupport 40, comprising prosthetic valve support 40 t, which comprisessupport-anchoring elements 66, comprising support-anchoring elements 66t, in accordance with some applications of the invention. Eachsupport-anchoring element 66 t comprises a coupling portion 70, coupledto upstream support portion 41 of support 40 t via length-adjustableholding element 600, comprising a telescopic holding element 600 t.Telescopic holding element 600 r comprises a plurality of portions,typically cylinders, which are slidable over and/or through each other.FIG. 18B shows telescopic holding element 600 t comprising twooverlapping cylinders. Sliding of the cylinders over each other adjuststhe distance between coupling portion 70 and upstream support portion41. Adjustment of this distance may be performed prior to implantationof prosthetic valve support 40 t, and/or during the implantationprocedure (e.g., after deployment of support 40 t).

Typically, telescopic holding element 600 t further comprises anotherelement (not shown), which controls and/or adjusts the sliding of thecylinders described hereinabove. For example, element 600 t may comprisea tension spring, such as those described with reference to FIGS. 17A-D,typically disposed inside the lumen defined by the overlappingcylinders. The combination of the tension spring with the overlappingcylinders combines the stretchability described with reference to FIGS.17A-D, with the rigidity described with reference to FIGS. 18A-B.

Reference is made to FIG. 19, which is a schematic illustration ofprosthetic valve support 40, comprising prosthetic valve support 40 v,which comprises support-anchoring elements 66, comprisingsupport-anchoring elements 66 v, in accordance with some applications ofthe invention. Each support-anchoring element 66 v comprises a couplingportion 70, coupled to upstream support portion 41 of support 40 v vialength-adjustable holding element 600, comprising length-adjustableholding element 600 v. Element 600 v comprises a strap 630 and a strapadjuster 632 (e.g., a buckle, a ladder lock, a tri-glide). Strap 630 andadjuster 632 are configured and arranged such that the distance betweencoupling portion 70 and upstream support portion 41 is adjustable bysliding adjuster 632 along strap 630, and/or by sliding at least part ofstrap 630 through adjuster 632. That is, strap 630 and strap adjuster632 are generally similar to the strap and adjustor of a bag, such as abackpack. Adjustment of element 600 v may be performed prior toimplantation of prosthetic valve support 40 v, and/or during theimplantation procedure (e.g., after deployment of support 40 v).

Non-limiting examples of materials which strap 630 and/or strap adjuster632 may comprise, include polyester, PTFE (e.g., ePTFE), nylon, cotton,nitinol, stainless steel, nickel cobalt, and cobalt chrome.

Reference is made to FIGS. 20A-F, which are schematic illustrations ofprosthetic valve support 40, comprising support-anchoring elements 66,comprising flexible support-anchoring elements 720, in accordance withsome applications of the invention. Elements 720 comprise a couplingportion 70 and a connector 540, which comprises (1) a flexible material722, such as a fabric (e.g., covering 440), pericardial tissue, and/or apolymer, and (2) one or more stiffening filaments 724. Filaments 724typically comprise a material that is stiffer and/or more resilient thanflexible material 722. For example, filaments 724 may comprise ametallic or plastic wire. Filaments 724 are coupled to material 722,such as by weaving and/or by gluing. The absolute and relativequantities and configurations of material 722 and filaments 724, may begenerated and/or selected so as to provide a desired stiffness of anelement 720. For example, an element 720 that comprises more and/or moredensely-woven stiffening filaments 724 may be selected for applicationsthat require a stiffer element 720. Conversely, an element 720 thatcomprises fewer and/or less densely-woven stiffening filaments 724 maybe selected for applications that require a more flexible element 720.FIGS. 20A-F show elements 720 comprising flexible support-anchoringelements 720 a-f, comprising various relative quantities of material 722and filaments 724, in accordance with respective applications of theinvention. These figures are not intended to limit the scope of theinvention but, rather, to illustrate the variability of the invention asa whole, and of elements 720 in particular.

For some applications, a kit is provided, containing a plurality ofprosthetic valve supports 40, each prosthetic valve support comprising aflexible support-anchoring element 720 having a different configurationof material 722 and filaments 724, and thereby a different flexibility(e.g., elements 720 a-720 f). A user typically selects a support 40 thatcomprises a support-anchoring element 720 of a desired configuration fora particular application.

For some applications, a kit is provided, containing (1) at least oneprosthetic valve support 40 (i.e., upstream support portion 41), and (2)a plurality of flexible support-anchoring elements 720, each element 720having a different configuration of material 722 and filaments 724, andthereby a different flexibility. A user typically (1) selects asupport-anchoring element 720 of a desired configuration for aparticular application, and (2) couples the selected element 720 to theupstream support portion 41.

For some applications, a kit is provided, containing (1) at least oneprosthetic valve support 40 (i.e., upstream support portion 41), (2) atleast one coupling portion 70, and (3) a plurality of connectors 540,each connector 540 having a different configuration of material 722 andfilaments 724, and thereby a different flexibility. A user typically (1)selects a connector 540 of a desired configuration for a particularapplication, and (2) couples the selected connector 540 to the couplingportion 70, and to the upstream support portion 41.

Reference is made to FIGS. 21A-C, which are schematic illustrations ofprosthetic valve 42, comprising prosthetic valve 42 j, in accordancewith some applications of the invention. Prosthetic valve 42 j comprisesat least one support-engaging element 422, comprising inflatablesupport-engaging element 426, disposed on the outer surface of primarystructural element 130 of prosthetic valve 42 j. FIGS. 21A-B showprosthetic valve 42 j comprising one annular inflatable support-engagingelement 426, disposed circumferentially around primary structuralelement 130. Typically, prosthetic valve support 40 comprises one ormore support-anchoring elements (not shown; e.g., support-anchoringelements 66, as described herein) which anchor the prosthetic valvesupport to native valve 23.

FIG. 21A shows prosthetic valve 42 j and prosthetic valve support 40.Following the deployment of prosthetic valve support 40 against theannulus of native valve 23, prosthetic valve 42 j is passed through thelumen of the prosthetic valve support as described hereinabove (e.g.,with reference to FIGS. 1A-H). As described hereinabove, prostheticvalve 42 j is typically less than fully expanded (e.g., prosthetic valve42 j is partially expanded) when it is passed through the lumen of theprosthetic valve. Accordingly, FIG. 21A shows prosthetic valve 42 j in apartially-expanded configuration.

FIG. 21B shows prosthetic valve 42 j having been expanded in the lumenof prosthetic valve support 40, such that inflatable support-engagingelement 426 is disposed distal (e.g., ventricularly) to prosthetic valvesupport 40. Element 426 is inflated (e.g., with saline) and therebyexpands, thereby increasing a longest transverse cross-sectional lengthof prosthetic valve 42 j, such that the transverse cross-sectionallength is longer than a longest transverse cross-sectional length of thelumen defined by prosthetic valve support 40. Thereby, inflatablesupport-engaging element 426 restricts proximal movement of prostheticvalve 42 j with respect to prosthetic valve support 40, therebyanchoring prosthetic valve 42 j to the distal side of prosthetic valvesupport 40, and to native valve 23.

Inflatable support-engaging element 426 is typically coupled toprosthetic valve 42 such that the prosthetic valve is compressible(i.e., crimpable) for delivery, as described hereinabove. For someapplications, inflatable support-engaging element 426 is coupled to theprosthetic valve using sutures. Typically, such sutures are arranged ina single circumferential suture line, so as to facilitate deformation(e.g., flattening) of element 426 during crimping of the prostheticvalve for delivery. For some applications, element 426 is coupled to theprosthetic valve using an adhesive.

FIG. 21C shows implant 30, comprising prosthetic valve support 40 andprosthetic valve 42 j, implanted at native valve 23, comprising mitralvalve 24. Support 40 is deployed against the proximal (i.e., atrial)surface of the annulus of the native valve, and is typically coupled tothe valve via support-anchoring elements 66 (not shown). Prostheticvalve 42 j is deployed in the lumen of support 40 such that, wheninflated, element 426 restricts proximal movement of the prostheticvalve with respect to support 40. This restriction, combined with thecoupling of support 40 to the native valve, couples implant 30 to thenative valve.

For some applications of the invention, prosthetic valve 42 j isdeployed in the lumen of support 40, such that element 426 is disposedon the proximal side of support 40. It is hypothesized that, when inthis position and inflated, element 426 restricts distal movement of theprosthetic valve with respect to the support.

For some applications of the invention, prosthetic valve 42 j isdeployed in the lumen of support 40, such that element 426 is planarwith upstream support portion 41 of the support, and such that at leastpart of element 426 is disposed proximal to portion 41, and at leastpart of element 426 is disposed distal to portion 41. It is hypothesizedthat, when in this position and inflated, element 426: (1) applies aradially-expansive force on support 40 (i.e., supplementsradially-expansive forces applied by prosthetic valve 42 on support 40),and (2) restricts proximal and distal movement of the prosthetic valvewith respect to the support.

Reference is made to FIGS. 22A-C, which are schematic illustrations ofthe implantation of implant 30, comprising prosthetic valve support 40and prosthetic valve 42, coupled by one or more (e.g., 2 or more, suchas 4) coupling leads 840 (e.g., coupling wires), in accordance with someapplications of the invention. For delivery, coupling leads 840 arecoupled to prosthetic valve support 40 and prosthetic valve 42. For someapplications, coupling leads 840 are slidably coupled to support 40and/or prosthetic valve 42. For example, within overtube 44, prostheticvalve 42 may be disposed proximally to support 40, and coupled tosupport 40 by being slidably coupled to coupling leads 840.

FIG. 22A shows prosthetic valve support 40, having been coupled tonative valve 23, comprising mitral valve 24. For example, support 40 maybe coupled to the native valve using techniques described herein (e.g.,via support-anchoring elements 66). Support 40 is coupled to couplingleads 840, which extend from support 40 to at least prosthetic valve 42,which remains disposed within overtube 44.

FIG. 22B shows prosthetic valve 42 having been deployed in the lumen ofsupport 40, and in the lumen of native valve 23, as described herein,mutatis mutandis. Coupling leads 840 extend from support 40, through aproximal portion (e.g., an upstream portion and/or proximal portion 110)of prosthetic valve 42, and into overtube 44. Typically, coupling lead840 comprises a plurality of teeth 846, typically disposed at a distalend of the coupling lead. A controller tube 844 is typically used toslide (e.g., push) ratchet housing 842 over coupling lead 840, and overteeth 846, such that the proximal portion of prosthetic valve 42 ispushed against support 40. Teeth 846 allow ratchet housing 842 to slideover coupling lead 840 in one direction, and inhibit (e.g., restrict)such sliding in another (e.g., the opposite) direction. Pushingprosthetic valve 42 against support 40 using controller tube 844 andratchet housing 842, thereby facilitates coupling of prosthetic valve 42to support 40. Thereby, sliding of ratchet housing 842 over couplinglead 840 facilitates coupling of the prosthetic valve to the prostheticvalve support.

Reference is made to FIG. 22C. Following the coupling of prostheticvalve 42 to prosthetic valve support 40, and thereby the implantation ofimplant 30 in native valve 23, coupling leads are typically cut at apoint proximal to ratchet housing 842, and overtube 44 is withdrawn fromthe subject.

Reference is made to FIGS. 23A-24, which are schematic illustrations ofprosthetic valve support 40, comprising prosthetic valve support 40 w,which is shaped to define at least one pocket 640, in accordance withsome applications of the invention. Prosthetic valve support 40 (i.e.,support 40 w) typically comprises a wire frame, such as an expandablewire frame. For some applications, the wire frame of support 40 w isshaped to define pocket 640. For some applications, the wire frame ofprosthetic valve support 40 (i.e., support 40 w) is generally coveredwith a covering (such as a fabric, e.g., as described herein). For someapplications, the covering may form at least one wall of pocket 640.

FIG. 23A shows an application of support 40 w, comprising upstreamsupport portion 41 that comprises a wire frame 642, generally coveredwith a covering 644. In this application, pocket 640 is generallyannular, and circumscribes the lumen defined by support 40 w (i.e., thelumen defined by upstream support portion 41 of support 40 w). That is,the lumen defined by support 40 w can be considered to be defined by twoholes: (1) a proximal (i.e., upper) hole defined by a proximal (i.e.,upper) wall of pocket 640, and (2) a distal (i.e., lower) hole definedby a distal (i.e., lower) wall of pocket 640. FIGS. 23A-24 show bothwalls of pocket 640 as having a generally similar depth. That is, alongest dimension of the distal hole is generally equal to the longestdimension of the proximal hole. For some applications, the two holes aregenerally not equally dimensioned. For example, to facilitate deploymentof prosthetic valve 42 and/or coupling of prosthetic valve 42 to support40 w, one of the holes that defines the lumen of support 40 w may have asmaller longest dimension than the other hole.

FIG. 23B shows prosthetic valve 42 comprising support-engaging elements422 (e.g., prosthetic valve 42 a comprising integral support-engagingelements 424, as described with reference to FIG. 8A), coupled toprosthetic valve support 40 w. Elements 422 typically define across-sectional area, the longest dimension of which is typically longerthan a transverse cross-sectional longest dimension of the lumen definedby prosthetic valve support 40 w (i.e., of the upper and/or lower holesdescribed with reference to FIG. 23A). During deployment, elements 422are placed within pocket 640. Thereby, in addition to theradially-expansive force that typically couples prosthetic valve 42 tosupport 40, the radially-protruding support-engaging elements 422restrict axial (i.e., proximal and distal) movement of prosthetic valve42 with respect to support 40 w, thereby anchoring prosthetic valve 42to support 40 w, and to native valve 23.

For some applications, prosthetic valve is provisionally expanded (1)sufficiently such that elements 422 protrude into pocket 420 and preventaxial movement of prosthetic valve 42, but (2) insufficiently forradially-expansive forces to fixedly couple the prosthetic valve toprosthetic valve support 40 w. In this configuration, a user may rotatethe prosthetic valve to a desired orientation, before finally allowingthe prosthetic valve to expand and become coupled to support 40 w.

FIG. 24 shows prosthetic valve 42, configured to comprise an expandedproximal portion 110 of primary structural element 130. Proximal portion110 defines a cross-sectional area with a longest length that is longerthan a transverse cross-sectional longest dimension of the lumen definedby prosthetic valve support 40 w (i.e., of the upper and/or lower holesdescribed with reference to FIG. 23A). During deployment, portion 110 isplaced within pocket 640. Thereby, in addition to the radially-expansiveforce that typically couples prosthetic valve 42 to support 40, portion110 restricts axial (i.e., proximal and distal) movement of prostheticvalve 42 with respect to support 40 w, thereby anchoring prostheticvalve 42 to support 40 w, and to native valve 23.

Reference is made to FIGS. 25A-E, which are schematic illustrations ofsequential steps in the use of a retrieval device 800, in accordancewith some applications of the invention. Retrieval device 800 comprisesa plurality of struts 804, and typically comprises a shaft 802, withwhich struts 804 are axially aligned, and around which the struts arecircumferentially disposed. A coupling element 805, such as a hook 806,is coupled to a middle portion of each strut.

Reference is made to FIGS. 25A-B. At some time subsequent toimplantation of a prosthetic valve (i.e., prosthetic valve 42), it maybe necessary and/or desirable to retrieve the prosthetic valve (i.e., toremove the prosthetic valve from the subject). Typically, retrievaldevice 800 is delivered to the site of the prosthetic valve (i.e., tothe native valve) in and/or using an overtube 808. Retrieval device 800is advanced toward prosthetic valve 42, and into the lumen defined bythe prosthetic valve.

FIG. 25C shows middle portions of struts 804 being extended radiallyoutward from shaft 802. Typically, one or more middle portions of struts804 are extended radially outward by reducing the distance between theproximal end and the distal end of each strut. For example, struts 804may be bent and/or folded. In the application of the invention shown inFIGS. 25A-E, retrieval device further comprises a cuff 810, coupled tothe proximal ends of struts 804, and slidably coupled to shaft 802.Movement of cuff 810 distally, reduces the distance between the proximaland distal ends of struts 804, thereby extending the middle portions ofthe struts radially outward.

FIG. 25D shows two, respectively orthogonal, cross-sectional views ofretrieval device 800 in the lumen of prosthetic valve 42. The middleportions of struts 804 have been extended radially outward, andtypically make contact with prosthetic valve 42. Prosthetic valve 42 istypically covered with a covering, which facilitates the desired flow ofblood through the prosthetic valve. The covering may comprisepolyethylene terephthalate (e.g., polyester), polytetrafluoroethylene(e.g., Teflon, ePTFE), pericardial tissue, or any other suitablematerial. Hooks 806 protrude through wire frame 812 of prosthetic valve42, and typically do not extend through covering 814. Following theextension of the middle portions of struts 804, coupling element 805 iscoupled to (e.g., hooks 806 are hooked around) wire frame 812 ofprosthetic valve 42. For example, hooks 806 are arranged to point in thesame direction as each other (e.g., such that all hooks point clockwise,or all hooks point anticlockwise). Following extension of the middleportions of struts 804, retrieval device 800 is rotated, such that hooks806 hook around wire frame 812, between the wire frame and covering 814.

Reference is made to FIG. 25E. Following coupling of coupling elements805 (i.e., hooks 806) to wire frame 812 of prosthetic valve 42, themiddle portions of struts 804 are retracted radially inward, i.e.,toward shaft 802. For example, the distance between proximal and distalends of struts 804 is increased, e.g., by sliding cuff 810 proximally.Because struts 804 are coupled to the wire frame, prosthetic valve 42 isdrawn radially inward. That is, prosthetic valve 42 is compressed (i.e.,re-crimped). Retrieval device 800 and prosthetic valve 42 are drawn intoovertube 808, and subsequently removed from the subject.

FIGS. 25A-E illustrate each strut 804 having two outwardly-extendablemiddle portions, in order to couple to, and compress prosthetic valve 42at/from two sites (i.e., a proximal site and a distal site). It ishypothesized that the use of device 800 comprising struts 804 withdifferent numbers and/or configurations of outwardly-extendable middleportions, allows the compression and/or retrieval of prosthetic valve ofdifferent dimensions and/or configurations.

Reference is again made to FIGS. 25A-E. For some applications, a hem 820is disposed within, and slidable through overtube 808. Hem 820 isadvanced out of the overtube during or after the advancement ofretrieval apparatus, and expands, such that a distal portion of the hemdefines a lumen that has a longer transverse cross-sectional area thanthat of overtube 808 (e.g., as shown in FIGS. 25B-C). When retrievaldevice 800 and prosthetic valve 42 are drawn into overtube 808, at leastproximal portions of the retrieval apparatus and prosthetic valve arefirst drawn into hem 820. Hem 820 facilitates the drawing in of theretrieval apparatus and prosthetic valve, by widening the effective openend of the overtube, and/or by reducing resistance between theprosthetic valve 42 and overtube 808. Although hem 820 is describedherein with respect to the use of retrieval device 800, it is to benoted that the scope of the present invention includes the use of hem820 in combination with any retrieval apparatus.

Reference is made to FIGS. 26A-C, which are schematic illustrations ofprosthetic valve support 40, comprising a braided prosthetic valvesupport 860, in accordance with some applications of the invention. Asdescribed hereinabove, support 40 is typically expandable, and typicallycomprises a shape-memory material. Support 860 typically furthercomprises a braided structure, comprising a plurality of intertwiningstrands 862. At least some regions of strands 862 are slidable past(e.g., over, under) each other. Typically, strands 862 comprise ashape-memory material such as, but not limited to, nitinol. In anexpanded state (i.e., uncompressed), support 40 is annular, and isshaped to define a lumen therethrough. For delivery, support 860 istypically advanced through the vasculature of the subject in acompressed configuration, e.g., within an overtube 44. FIG. 26A showssupport 860 being deployed from overtube 44 at native valve 23 (i.e.,proximal to the native valve). Typically, support 860 is deployedproximal to the native valve.

FIG. 26B shows sequential illustrations of the expansion of support 860as it is deployed from overtube 44. Support 860 is typically coupled toa restricting element, such as drawstring 864, in a manner that at leastpartly restricts expansion of the support. FIG. 26B shows drawstring 864threaded through a plurality of rings 866, disposed at the proximal endof support 860, whereby both ends of drawstring 864 are disposedproximal to the open distal end of overtube 44 (e.g., within overtube44, and/or outside the body of the subject). Drawstring 864 therebyforms a closed loop that is coupled to rings 866 and, thereby, tosupport 860. Once support 860 has been fully ejected from overtube 44,tension on drawstring 864 typically restricts expansion of support 860.Subsequently, at least one end of drawstring 864 is moved distally(i.e., the drawstring is at least partially loosened), such that support860 moves toward its uncompressed, expanded shape. When support 860 issuccessfully positioned (i.e., when a user determines that the supportis in the desired position), one end of drawstring 864 is released,typically in combination with drawing (i.e., retracting) the other endof drawstring 864 proximally, thereby releasing support 860 from thedrawstring.

FIG. 26C shows prosthetic valve support 860 in its fully-expandedconfiguration, against the proximal (i.e., atrial) side of the annulusof native valve 23. One end of drawstring 864 has been released, and thedrawstring is shown being retracted proximally.

Throughout the deployment of prosthetic valve support 860, until therelease of one end of drawstring 864, support 860 may be retrieved bymoving drawstring 864 proximally (i.e., pulling the drawstring). Pullingthe drawstring (1) tightens the loop formed by the drawstring, therebybringing rings 866 closer to each other, and compressing the proximalportion of support 860, and (2) draws support 860 into overtube 44.Thus, a user can determine if and/or when to release support 860,throughout the deployment procedure.

Reference is made to FIGS. 27A-D, which are schematic illustrations ofdelivery apparatus 880, and the use thereof, in accordance with someapplications of the invention. FIGS. 27A-D show apparatus 880 being usedto deliver and deploy a medical device 150, comprising prosthetic valve42, to native valve 23. Apparatus 880 comprises a plurality of controlfilaments 882, disposed and slidable within respective guide elements,such as rail-pairs 884 (e.g., between individual rails thereof).Rail-pairs 884 are typically extendable. For example, rail-pairs 884 maycomprise sections that are slidable over and/or through each other, suchthat the rail-pairs are telescopically extendable. Apparatus 880typically comprises a core 886, from which rail-pairs 884 typicallyprotrude radially, such that extension of rail-pairs 884 comprisesoutwardly-radial extension of the rail-pairs from core 886.

Apparatus 880 has a contracted configuration and an extendedconfiguration, is typically reversibly movable between these twoconfigurations, and is further typically movable into continuousconfigurations between the contracted and extended configurations. FIG.27A shows apparatus 880 in the contracted configuration. In thecontracted configuration, rail-pairs 884 are typically telescopicallyretracted, such that apparatus 880 is disposable in delivery tube 60.That is, in the contracted configuration, a longest length of atransverse cross-section of apparatus 880 is smaller than a longestlength of a transverse cross-section of delivery tube 60.

FIG. 27B shows medical device 150, comprising prosthetic valve 42, beingdeployed from delivery tube 60, at native valve 23, using apparatus 880.Apparatus 880 is coupled to a portion (e.g., a proximal portion) ofprosthetic valve 42, and is disposed within delivery tube 60. Apparatus880 is thereby not visible in FIG. 27B. A distal portion of prostheticvalve 42 has been exposed from delivery tube 60, and has begun to expandtoward its expanded configuration. Typically, prosthetic valve 42 ismoved with respect to delivery tube 60 (e.g., is pushed out of thedelivery tube) by core 886, which thereby acts as a pushing member.

As described hereinabove, prosthetic valve 42 typically comprises ashape-memory material, and expands toward its expanded configuration asit is exposed from delivery tube 60. In the application of the inventiondescribed with reference to FIGS. 27A-D, apparatus 880 typicallycontrols this expansion. Control filaments 882 are typically coupled(e.g., slidably coupled) to prosthetic valve 42, e.g., via respectivecoupling pins 888, which are couplable to prosthetic valve 42, andslidably couplable to control filaments 882. Release wires 892facilitate the coupling of control filaments 882 to prosthetic valve 42,e.g., by facilitating the coupling of coupling pins 888 to prostheticvalve 42.

Control filaments 882 (e.g., proximal portions thereof) are distallyadvanceable, and proximally retractable, through a control tube 890,e.g., using a control unit external to the subject. Control filaments882 are slidably couplable to core 886 and/or control tube 890, such asbeing slidable through respective conduits (e.g., holes) in the core orthe control tube. The expansion of apparatus 880, and thereby that ofprosthetic valve 42, is restricted and/or facilitated (e.g., controlled)by the distal advancement and/or proximal retraction of controlfilaments 882. In the application of the invention illustrated in FIGS.27A-D, control filaments 882 form respective loops. The size of theloops is increased when the control filaments are distally advanced, andreduced when the control filaments are proximally retracted. When theloops are small, control filaments 882 restrict expansion of prostheticvalve 42. Distal advancement of control filaments 882, and the resultingenlargement of the loops formed thereof, facilitates the expansion ofprosthetic valve 42.

FIG. 27C shows apparatus 880 in its expanded configuration. FIG. 27Dshows apparatus 880 in its expanded configuration, coupled to prostheticvalve 42, during the deployment of the prosthetic valve. Rail-pairs 884protrude radially from core 886, and control filaments 882 remaincoupled to the prosthetic valve, facilitated by release wires 892, asdescribed hereinabove. Rail-pairs 884 typically facilitate (e.g., guide)the expansion of prosthetic valve 42.

When prosthetic valve 42 is successfully positioned (i.e., when a userdetermines that the prosthetic valve is in the desired position),prosthetic valve 42 is released from control filaments 882, e.g., bypulling release wires 892 proximally. Release of prosthetic valve 42allows (1) the prosthetic valve to expand further (e.g., until itcouples to, and is restricted by, support 40), and/or (2) controlfilaments 882 to be retracted, and rail-pairs 884 to be telescopicallyretracted, such that apparatus 880 is retractable into delivery tube 60.

For some applications, rail-pairs 884 are biased toward moving into thecontracted configuration thereof, are pulled radially outward by theexpansion of prosthetic valve 42, and automatically return to thecontracted configuration upon release of the prosthetic valve. Forexample, the rail-pairs may provide a contractive force, and theprosthetic valve may provide an expansive force that is sufficient toovercome the contractive force, and thereby to pull the rail-pairsradially outward. Upon release of the prosthetic valve, the contractiveforce automatically returns the rail-pairs to the contractedconfiguration thereof. Alternatively or additionally, rail-pairs 884 maybe actively controllable (e.g., extracorporeally) by a user.

For some applications of the invention, proximal portions of controlfilaments 882 are coupled to each other (e.g., fixedly coupled to eachother, such as adhered and/or welded to each other), such that theplurality of control filaments are synchronously distally advanceable,and synchronously proximally retractable, e.g., via a control rod and/orcontrol unit.

For some applications of the invention, proximal portions of releasewires 892 are coupled to each other (e.g., fixedly coupled to eachother, such as adhered and/or welded to each other), such that theplurality of release wires are pullable synchronously, e.g., via acontrol rod and/or control unit, thereby facilitating synchronousrelease of control filaments 882.

Throughout the deployment of prosthetic valve 42 using apparatus 880,until the release of the prosthetic valve from control filaments 882,prosthetic valve 42 may be re-compressed (e.g., for repositioning and/orretrieval into delivery tube 60) by proximally retracting controlfilaments 882. Thus, a user can determine if and/or when to releaseprosthetic valve 42, throughout the deployment procedure. That is,prosthetic valve 42 is recompressible (i.e., the expansion of prostheticvalve 42 is at least in part reversible) by proximal retraction ofcontrol filaments 882.

That is, (1) control filaments 882 are slidable through conduits of core886, and reversibly couplable to prosthetic valve 42, and (2) deliveryapparatus 880 is configured to control and/or facilitate (a) expansionof prosthetic valve 42, by the control filaments being advanced distallythrough the conduits, and (b) recompression of prosthetic valve 42, bythe control filaments being retracted proximally through the conduits.

Reference is made to FIGS. 28A-30B, which are schematic illustrations oftechniques for replacement of a prosthetic valve, in accordance withsome applications of the invention. It is noted that in the context ofthe present patent application, the term “replacement” with respect to aprosthetic valve includes both (a) placement at a valve site of a newprosthetic valve while removing or disabling a prosthetic valve that wasalready at the valve site, as well as (b) placement of a new prostheticvalve at the valve site without removing or disabling a prosthetic valvethat was already at the site.

Prosthetic cardiac valves typically require replacement after a duration(e.g., after between 1 month and 10 years, such as after between 1 and 5years). For example, the condition of the subject may change, componentsof the prosthetic valve (e.g., prosthetic valve leaflets, sutures,frame) may suffer fatigue, and/or tissue growth may block blood flow orotherwise interfere with prosthetic valve function.

The prosthetic valve supports described with reference to FIGS. 28A-30Bare typically couplable to the native valve using techniques describedherein for coupling other prosthetic valve supports to the native valve.For example, the prosthetic valve supports described with reference toFIGS. 28A-30B may comprise tissue-engaging elements (e.g.,support-anchoring elements), such as those described herein. Similarly,other prosthetic valve supports described herein may comprise theupstream support portions and/or the cylindrical elements of theprosthetic valve supports described with reference to FIGS. 28A-30B.

Reference is now made to FIGS. 28A-D. FIGS. 28A-B show implant 30,comprising prosthetic valve 42 coupled to prosthetic valve support 40,such as described hereinabove with reference to the implantation ofimplant 30 (e.g., with reference to FIGS. 1A-H). FIG. 28A shows a sideview and FIG. 28B shows a top view. At such a time that it is deemednecessary and/or desirable to replace prosthetic valve 42, a secondprosthetic valve 42′ is delivered to the lumen of the first prostheticvalve, and deployed therein. Generally, delivery and deployment ofprosthetic valve 42′ is performed using similar techniques to those usedto deploy prosthetic valve 42.

FIGS. 28C-D show second prosthetic valve 42′ in an expandedconfiguration within the lumen of prosthetic valve 42. FIG. 28C shows aside view and FIG. 28D shows a top view. Both prosthetic valve 42 andprosthetic valve 42′ comprise valve components, typically valve leaflets660, disposed in the lumen of the prosthetic valve. As it expands,prosthetic valve 42′ typically pushes aside leaflets 660 of prostheticvalve 42. Prosthetic valve 42′ exerts radially-expansive forces againstthe inner surface of prosthetic valve 42, thereby coupling prostheticvalve 42′ to prosthetic valve 42. In some applications, leaflets 660 aresandwiched between prosthetic valve 42 and prosthetic valve 42′ (i.e.,between the primary structural elements 130 of the prosthetic valves).In some applications, leaflets 660 facilitate sealing between the twoprosthetic valves. Following the deployment of prosthetic valve 42′,leaflets 660′ of prosthetic valve 42′ begin to function, therebyreplacing the function of leaflets 660. Typically, diameter d2 ofdeployed prosthetic valve 42′ is smaller than diameter d1 of deployedprosthetic valve 42. Typically, the difference in diameter is caused atleast in part by prosthetic valve 42 restricting the expansion ofprosthetic valve 42′.

Reference is now made to FIGS. 29A-F. FIGS. 29A-B show implant 30,comprising prosthetic valve 42 coupled to prosthetic valve support 40,comprising prosthetic valve support 40 x. FIG. 29A shows a side view andFIG. 29B shows a top view. As described hereinabove, prosthetic valvesupport 40 is generally annular, and typically comprises a wire frameand/or a shape-memory material. For some applications, the wire frame ofprosthetic valve support 40 (i.e., wire frame 672 of support 40 x) isgenerally covered with covering 440 (such as a fabric, e.g., asdescribed herein). Support 40 x typically comprises a weak zone 670 thatcircumscribes the lumen defined by the support (i.e., the lumen definedby upstream support portion 41 of support 40 x).

For some applications, wire frame 672 does not extend into weak zone670; rather the weak zone only comprises covering 440. For someapplications, a stretchable and/or breakable reinforcing-wire 674 isdisposed at or near inner edge 68 of upstream support portion 41 ofsupport 40 x. For some applications, wire frame 672 has a differentstructure in weak zone 670 than in other regions of upstream supportportion 41 of support 40 x. For example, wire frame 672 may comprisefewer struts in weak zone 670.

FIG. 29C shows an expanding device, such as a balloon 678, having beendelivered to the lumen of prosthetic valve 42, and being used to expand(e.g., to enlarge) the lumen of the prosthetic valve and the lumen ofprosthetic valve support 40 x. FIG. 29D shows a transversecross-sectional view of support 40 x and prosthetic valve 42, followingthe expansion of the lumen of the prosthetic valve with balloon 678. Atsuch a time that it is deemed necessary and/or desirable to replaceprosthetic valve 42, balloon 678 is delivered to the prosthetic valveand inflated (e.g., using saline), such that it applies aradially-expansive force, from within the lumen of prosthetic valve 42,to the prosthetic valve and support 40 x. Typically, theradially-expansive force applied by the balloon is greater than theradially-expansive force applied by prosthetic valve 42 on support 40(i.e., support 40 x), that typically couples prosthetic valve 42 tosupport 40. For some applications, balloon 678 is shaped to define alumen, so that blood can continue to flow while the balloon is expanded.For some such applications, balloon 678 comprises a temporary prostheticvalve (i.e., one or more temporary prosthetic valve leaflets), disposedin the lumen of the balloon, and configured to further facilitatecontinued blood flow while the balloon is expanded.

The radially-expansive force applied by balloon 678 increases the lumenof prosthetic valve 42, typically by increasing the lumen of support 40x by deforming (e.g., crushing) weak zone 670. For example, a materialwhich weak zone 670 comprises may be compressed, broken, bent, stretchedand/or torn (e.g., reinforcing wire 674 may be broken and/or covering440 may be stretched and/or torn). Balloon 678 is subsequently removedfrom the subject. Typically, leaflets 660 continue to function at leastin part until second prosthetic valve 42′ is deployed.

For some applications, leaflets 660 are disposed in a portion ofprosthetic valve 42 that is distal (i.e., ventricular) to the portion ofprosthetic valve 42 that is coupled to prosthetic valve support 40 x.For these applications, balloon 678 is typically disposable in aproximal portion of valve 42, and thereby may be used to increase thelumen of prosthetic valve 42, without damaging (e.g., crushing) leaflets660.

FIGS. 29E-F show second prosthetic valve 42′ in an expandedconfiguration within the lumen of prosthetic valve 42. FIG. 29E shows aside view and FIG. 29F shows a top view. Prosthetic valve 42′ exertsradially-expansive forces against the inner surface of prosthetic valve42, thereby coupling prosthetic valve 42′ to prosthetic valve 42.Because the lumen of prosthetic valve 42 is initially expanded, asdescribed hereinabove, a diameter d3 of the lumen defined by prostheticvalve 42′ may not be smaller than the diameter d1 of the lumenoriginally defined by prosthetic valve 42 (i.e., d3 may be at least asgreat as d1). For example, diameter d3 may be equal to, or larger than,diameter d1.

Reference is again made to FIGS. 28A-29F. For some applications of theinvention, prosthetic valve 42′ comprises a second prosthetic valve 42.That is, a second (i.e., new) prosthetic valve 42 is used to replace afirst prosthetic valve 42. Alternatively, prosthetic valve 42′ may bedifferent to prosthetic valve 42. For some applications, prostheticvalve 42′ may comprise a sealing element, such as a circumferential seal(e.g., a soft material and/or a balloon), that facilitates sealingand/or coupling between prosthetic valve 42′ and prosthetic valve 42.For some applications, prosthetic valve 42′ comprises protruding barbs,which facilitate coupling between the two prosthetic valves.

For some applications, a distal portion of prosthetic valve 42′ definesa cross-sectional area with a longest length that is longer than atransverse cross-sectional longest dimension of the lumen defined byprosthetic valve 42 (i.e., defined by primary structural element 130 ofprosthetic valve 42). During deployment of prosthetic valve 42′, thedistal portion is placed distal to the open distal end of prostheticvalve 42 (i.e., in the ventricle). Thereby, in addition to theradially-expansive force that typically couples prosthetic valve 42′ toprosthetic valve 42, the distal portion restricts proximal movement ofprosthetic valve 42′ with respect to prosthetic valve 42, therebyanchoring prosthetic valve 42′ to prosthetic valve 42, and to nativevalve 23.

Reference is made to FIGS. 30A-B, which are schematic illustrations ofimplant 30, comprising prosthetic valve 42 and prosthetic valve support40 y, being restored by the addition of a second prosthetic valve 42′,in accordance with some applications of the invention. Prosthetic valvesupport 40 y comprises upstream support portion 41 coupled to acylindrical element 690 that is typically configured to extend distallythrough native valve 23. Alternatively, cylindrical element 690 may beconfigured to extend away from the native valve. Prosthetic valvesupport 40 y is typically couplable to the native valve using techniquesdescribed herein for coupling other prosthetic valve supports to thenative valve. For example, prosthetic valve support 40 y may comprisetissue-engaging elements (e.g., support-anchoring elements). Cylindricalelement 690 is typically configured to (1) facilitate coupling ofprosthetic valve support 40 y to the native valve, and/or sealingtherebetween, (2) to facilitate coupling of prosthetic valves toprosthetic valve support 40 y, and/or sealing therebetween, and/or (3)to push aside native leaflets 82 of native valve 23.

FIG. 30A shows prosthetic valve 42 having been deployed in the lumen ofprosthetic valve support 40 y. Typically, prosthetic valve 42 isdeployed in a distal (i.e., more ventricular and/or downstream) portionof the lumen.

FIG. 30B shows prosthetic valve 42′ having been deployed in the lumen ofprosthetic valve support 40 y. At such a time that it is deemednecessary and/or desirable to perform a replacement of prosthetic valve42, prosthetic valve 42′ is delivered to, and deployed in, anotherportion of prosthetic valve support 40 y. Typically, prosthetic valve42′ is deployed in a portion of the lumen that is proximal to (e.g.,upstream of) prosthetic valve 42. That is, prosthetic valve support 40 yis configured to receive, at a first period, a first prosthetic valve ata first longitudinal portion of the lumen of cylindrical element 690,and to receive, at a second period, a second prosthetic valve at asecond longitudinal portion of the lumen.

For some applications, prosthetic valve 42 continues to function atleast in part, and at least temporarily. That is, prosthetic valve 42and prosthetic valve 42′ operate generally simultaneously. For someapplications, prosthetic valve 42 is disabled in conjunction withdeployment of prosthetic valve 42′. For example, leaflets 660 ofprosthetic valve 42 may be disabled, removed and/or restrained, by usinga separate device (not shown) and/or by using a part (e.g., an extendingelement; not shown) of prosthetic valve 42′.

For some applications, the primary structural element 130 of prostheticvalve 42′ is longer than the primary structural element of prostheticvalve 42, and the leaflets of prosthetic valve 42′ are disposed in aproximal portion of the primary structural element thereof. A distalportion of the primary structural element of prosthetic valve 42′ isdeployed in the lumen of prosthetic valve 42, such that the leaflets ofprosthetic valve 42 are crushed upon expansion of prosthetic valve 42′.

Reference is made to FIGS. 31A-33C, which are schematic illustrations ofdelivery tube 60, in accordance with some applications of the invention.Deployment of a medical device 150, such as prosthetic valve 42, asdescribed with reference to FIGS. 1A-H, typically comprises proximalmovement of delivery tube 60 relative to prosthetic valve 42, asdescribed hereinabove. Immediately prior to the release of prostheticvalve 42 from the delivery tube, the length of the deliverytube-plus-prosthetic valve may be double or more than that of thedelivery tube or prosthetic valve alone. For some applications, thisextra length can hinder the movement of, and removal of, the deliverytube from the body. A delivery tube that takes up less room duringand/or following deployment of prosthetic valve 42 would thereby beadvantageous.

FIGS. 31A-C show delivery tube 60, comprising a flexible delivery tube60 b being used to deliver prosthetic valve 42, in accordance with someapplications of the invention. Delivery tube 60 b comprises a flexiblematerial, such as a fabric or polymer. FIG. 31A shows prosthetic valve42 in a compressed (i.e., crimped) configuration within delivery tube 60b. Prosthetic valve 42 exerts an expansive force on tube 60 b, and tube60 b provides a reciprocal compressive force on prosthetic valve 42.Delivery tube 60 b is typically not rigid; rather prosthetic valve 42provides (i.e., dictates) the shape to which the delivery tube conforms.That is, prosthetic valve 42 functions as a scaffold on which deliverytube 60 b is disposed.

FIG. 31B shows prosthetic valve 42 partially deployed from delivery tube60 b. For example, prosthetic valve 42 may be pushed distally out of thedelivery tube using a pushing member (e.g., pushing member 140). FIG.31C shows prosthetic valve 42 fully deployed from delivery tube 60 b.Prosthetic valve 42 has expanded toward its expanded configuration. Thereciprocal expansive and compressive forces are thereby no longerexerted, and delivery tube 60 b no longer conforms to a rigid shape.That is, delivery tube 60 b becomes flaccid, facilitating its removalfrom the subject. For example, delivery tube 60 b may be moved aroundcorners and/or into an overtube such as a catheter.

FIGS. 32A-C show delivery tube 60, comprising a compressible deliverytube 60 c being used to deliver prosthetic valve 42, in accordance withsome applications of the invention. Delivery tube 60 c comprises aflexible material, such as a fabric or polymer, and one or more pullingwires 740. Delivery tube 60 c typically further comprises an aperturering 742. FIG. 32A shows prosthetic valve 42 in a compressed (i.e.,crimped) configuration within delivery tube 60 c. Prosthetic valve 42exerts an expansive force on tube 60 c, and tube 60 c provides areciprocal compressive force on prosthetic valve 42. Delivery tube 60 cis typically not rigid; rather prosthetic valve 42 provides (i.e.,dictates) the shape to which the delivery tube conforms. That is,prosthetic valve 42 functions as a scaffold on which delivery tube 60 cis disposed. Pulling wires 740 extend from a proximal site (e.g.,outside the subject) and are coupled to a distal portion of deliverytube 60 c (e.g., to aperture ring 742).

FIG. 32B shows prosthetic valve 42 partially deployed from delivery tube60 c. Typically, following placement of delivery tube 60 c (and therebyprosthetic valve 42) in the lumen of native valve 23, pulling wires 740are pulled, drawing the distal portion of the delivery tube (e.g.,aperture ring 742) proximally. Delivery tube 60 c is thereby compressed(i.e., shortened) and a distal portion of prosthetic valve 42 isexposed, and typically expands at least in part responsively. Forexample, a proximal end of delivery tube 60 c may be generally closed,such that compressing (i.e., shortening) of the delivery tube, exposesthe distal portion of prosthetic valve 42 from the distal end of thedelivery tube. FIG. 32C shows prosthetic valve 42 fully deployed fromdelivery tube 60 c. Prosthetic valve 42 has expanded toward its expandedconfiguration. Delivery tube 60 c is generally compressed such that ithas a length of less than 50% (e.g., less than 30%, such as less than10%) of its length when containing prosthetic valve 42, therebyfacilitating its removal from the subject. For example, delivery tube 60c may be moved around corners and/or into an overtube such as acatheter.

FIGS. 33A-C show delivery tube 60, comprising a dismantling deliverytube 60 d being used to deliver prosthetic valve 42, in accordance withsome applications of the invention. Delivery tube 60 d comprises aflexible material, such as a fabric or polymer, and a pullstring 750.FIG. 33A shows prosthetic valve 42 in a compressed (i.e., crimped)configuration within delivery tube 60 d. Prosthetic valve 42 exerts anexpansive force on tube 60 d, and tube 60 d provides a reciprocalcompressive force on prosthetic valve 42. Delivery tube 60 d istypically not rigid; rather prosthetic valve 42 provides (i.e.,dictates) the shape to which the delivery tube conforms. That is,prosthetic valve 42 functions as a scaffold on which delivery tube 60 dis disposed. Pullstring 750 is coupled to the flexible material ofdelivery tube 60 d, typically along the length of the delivery tube.Typically, delivery tube 60 d comprises a sheet of the flexiblematerial, held in a generally cylindrical shape by pullstring 750. Forexample, pullstring 750 may weave between two parts of the flexiblematerial, stitching them together. Alternatively, pullstring 750 may becoupled to the two parts of the flexible material via a weakened (e.g.,perforated) join.

FIG. 33B shows prosthetic valve 42 partially deployed from delivery tube60 d. Typically, following placement of delivery tube 60 d (and therebyprosthetic valve 42) in the lumen of native valve 23, pullstring 750 ispulled, decoupling the two parts of the flexible material, and therebyopening delivery tube 60 d. Typically, regions of prosthetic valve 42expand as regions of delivery tube 60 d are opened. FIG. 33C showsprosthetic valve 42 fully deployed from delivery tube 60 d. Prostheticvalve 42 has expanded toward its expanded configuration. Pullstring 750has been pulled sufficiently, such that the flexible material ofdelivery tube 60 d becomes a generally open sheet. That is, deliverytube 60 d typically loses its cylindrical shape and becomes flaccid,thereby facilitating its removal from the subject. For example, deliverytube 60 d may be moved around corners and/or into an overtube such as acatheter.

Reference is made to FIG. 34, which is a schematic illustration ofprosthetic valve 42, comprising a tissue-engaging element 62, comprisinga leaflet-engaging element 760, coupled to a distal portion of primarystructural element 130 of the prosthetic valve, in accordance with someapplications of the invention. For some applications, leaflet-engagingelement 760 is similar in structure to a valve-anchoring element 64,such as a loop-shaped valve-anchoring element 200. Element 760 ispositioned and configured so as to engage a single leaflet, typicallythe anterior leaflet, of native valve 23. The engagement of the leafletis hypothesized to reduce undesired interference with blood flow.Specifically, holding the anterior leaflet clear of the LVOT ishypothesized to reduce interference with blood flowing from the leftventricle into the aorta.

Although element 760 is described with reference to FIG. 34 as beingcoupled to the primary structural element of prosthetic valve 42, it isto be noted that the scope of the present invention includes an element760 being additionally or alternatively coupled to prosthetic valvesupport 40.

Reference is made to FIGS. 35A-C, which are schematic illustrations ofsequential steps in the implantation of prosthetic valve 42, andprosthetic valve support 40, comprising prosthetic valve support 40 z,in accordance with some applications of the invention. As describedhereinabove, support 40 comprises an upstream support portion 41 whichis shaped to define a lumen. During implantation of implant 30,prosthetic valve 42 is deployed in this lumen. As described herein, forsome applications of the invention, support 40 is coupled to nativevalve 23 prior to delivery and/or deployment of prosthetic valve 42. Forexample, support 40 may comprise tissue-engaging elements 62, comprisingsupport-anchoring elements 66 (not shown in FIGS. 35A-C). In someapplications, support 40 and/or the coupling thereof to native valve 23,interferes with the functioning of leaflets 82 of the native valve. Forexample, in some applications, support 40 is coupled to the native valvevia support-anchoring elements 66 engaging (i.e., coupling to) leaflets82, thereby disrupting native valve function. For further example, insome applications, elements 66 move leaflets 82, so as to sandwich theleaflets against prosthetic valve 42. For applications such as these,there is typically a period after the coupling of support 40 to thenative valve, and before deployment of prosthetic valve 42, that thenative valve has significantly reduced functionality. Prosthetic valvesupport 40 z comprises one or more temporary valve components, such astemporary leaflets 700, and advantageously provides temporary valvefunctionality during this period.

FIG. 35A shows prosthetic valve support 40 z, which comprises one ormore temporary valve components, such as temporary leaflets 700,typically disposed in the lumen defined by support 40 z. Leaflets 700provide temporary valve functionality to support 40 z, therebyfacilitating pumping of blood by the heart in the absence of nativevalve function. Temporary leaflets 700 may comprise a biologicalmaterial, such as pericardial tissue, and/or a synthetic material, suchas silicone, polyethylene terephthalate (e.g., polyester), and/orpolytetrafluoroethylene (e.g., Teflon). Temporary leaflets are typicallycoupled to upstream support portion 41 using sutures. It is noted that,although prosthetic valve support 40 z is illustrated in FIGS. 35A-C asnot comprising tissue-engaging elements such as support-anchoringelements 66, prosthetic valve support 40 z typically does comprisesupport-anchoring elements 66, such as those described elsewhere herein.

FIG. 35B shows prosthetic valve 42 being deployed in the lumen ofsupport 40 z. For some applications, prosthetic valve 42 is deployed asdescribed with reference to FIGS. 1A-H, mutatis mutandis. For someapplications, prosthetic valve 42 is deployed as described withreference to FIGS. 15A-L, mutatis mutandis. As it expands, prostheticvalve 42 typically pushes aside temporary leaflets 700.

FIG. 35C shows prosthetic valve 42 having been fully deployed (i.e.,expanded) in the lumen of support 40 z. In some applications, leaflets700 are sandwiched between prosthetic valve 42 and support 40 z. In someapplications, leaflets 700 facilitate sealing between prosthetic valve42 and support 40 z. As prosthetic valve 42 is deployed, it begins tofunction, thereby replacing the temporary valve functionality ofleaflets 700. Thereby, the techniques described with reference to FIGS.35A-C provide ongoing valve functionality throughout the implantation ofa prosthetic valve.

Reference is made to FIGS. 36A-D, which are schematic illustrations ofprosthetic valve support 40, comprising a prosthetic valve support 1040,in accordance with some applications of the invention. For someapplications of the invention, prosthetic valve support 1040 isanalogous to other prosthetic valve supports described herein. For someapplications of the invention, prosthetic valve support 1040 comprisesprosthetic valve support 40. Support 1040 comprises upstream supportportion 41, which is shaped to define a lumen. Support 1040 comprisesone or more support-anchoring elements 900 and one or more stabilizinglegs 910. Typically, support 1040 comprises two support-anchoringelements 900 and two stabilizing legs 910. Typically, support-anchoringelements 900 and stabilizing legs 910 are coupled to inner edge 68 ofupstream support portion 41. For some applications of the invention,support-anchoring elements 900 are embodiments of support-anchoringelements 66, which are embodiments of tissue-engaging elements 62, asdescribed hereinabove. For some applications of the invention,stabilizing legs 910 are embodiments of support-anchoring elementsand/or of tissue-engaging elements 62, as described hereinabove.

FIG. 36A shows a lower side view of support 1040. Typically,support-anchoring elements 900 comprise clips and/or clip functionality.Elements 900 are illustrated in FIG. 36A as generic clips, and maycomprise any of the clips described herein, and/or any other clips thatare couplable to the leaflets of the native valve (e.g.,support-anchoring elements 900 a and 900 b and the clip functionalitiesthereof, described hereinbelow with reference to FIGS. 37A-H, and38A-H). For some applications of the invention, support-anchoringelement 900 comprises two clip elements, (1) coupled at a couplingpoint, and (2) between which, during implantation, leaflets 82 of thenative valve are typically clamped. Clamping of a leaflet between thetwo clip elements couples element 900 to the leaflet. Typically, oneclip element is substantially immobile, and the other clip element is(1) biased to assume a first configuration, and (2) movable between thefirst configuration and another configuration.

Element 900 typically has (1) an open configuration, in which leaflets82 of the native valve may be moved between the two clip elements, and(2) a closed configuration, in which the clip elements typically clamp(i.e., couple to) the leaflets. Element 900 is typically moved betweenthe open and closed configurations thereof (i.e., is opened and closed)by moving at least one clip element between the first configurationthereof, and the other configuration thereof.

Typically, the clip elements are disposed at a distal portion of eachsupport-anchoring element 900, and a proximal portion (e.g., a proximalend) of each element 900 is coupled to upstream support portion 41.Typically, support-anchoring elements 900 have a length (i.e., adistance from (1) the point of coupling of the element 900 to upstreamsupport portion 41, to (2) a distal end of the element 900) of between 3and 20 mm, (e.g., between 5 and 12 mm). Typically, the proximal portionhas a length (i.e., a distance between (1) the point of coupling ofelement 900 to upstream support portion 41, and (2) a clip element) ofbetween 2 and 10 mm, (e.g., between 2 and 8 mm).

Support 1040 typically comprises two support-anchoring elements 900 andtwo stabilizing legs 910. Typically, elements 900 and legs 910 aredisposed at inner edge 68 in an alternating manner, i.e., such that eachleg 910 is between two elements 900, and each element 900 is between twolegs 910.

Typically, stabilizing leg 910 is longer than support-anchoring element900. That is, a distance between (1) a coupling point 911 of upstreamsupport portion 41 and a stabilizing leg 910 and (2) a distal end of thestabilizing leg, is typically greater than a distance between (1) acoupling point of upstream support portion 41 and an element 900 and (2)a distal end of the element 900. Typically, stabilizing leg 910 has alength of between 5 mm and 30 mm (e.g., between 5 mm and 20 mm), and awidth of between 0.4 mm and 5.0 mm.

For some applications of the invention, each stabilizing leg 910comprises a proximal portion 912 and a distal portion 914, whereby theproximal portion is coupled at coupling point 913 between thestabilizing leg and the distal portion. For some such applications,stabilizing leg 910 comprises a bend, such that an axis defined bydistal portion 914 is divergent to an axis defined by the proximalportion. Typically, proximal portion 912 has a length of between 5 mmand 20 mm.

Typically, stabilizing legs 910 have a stabilizing configuration, inwhich they stabilize prosthetic valve support 1040 at the native valve.Typically, in the stabilizing configuration, the proximal portion 912 ofeach leg 910 is disposed on a plane between (1) a plane that isorthogonal to a plane defined by upstream support portion 41, and (2) aposition in which the leg touches a part of upstream support portion 41that is peripheral to inner edge 68. That is, in the stabilizingconfiguration, proximal portion 912 typically forms an acute angle witha portion of upstream support portion 41.

Stabilizing legs 910 are hypothesized to increase the stability ofprosthetic valve support 1040 at the native valve. For example, legs 910are hypothesized to at least partly inhibit (1) lateral rotation (i.e.,rotation around an atrial-ventricular axis) of the prosthetic valvesupport, and/or (2) movement of the parts of upstream support portion 41that are disposed against the proximal (e.g., atrial) side of the nativevalve, from moving away from, or through, the native valve. Followingdeployment (e.g., implantation) of prosthetic valve 42, legs 910 arefurther hypothesized to reduce rolling movement (e.g., movement around alateral axis, e.g., an axis between two elements 900, such as an axisthat is generally orthogonal to an axis between the stabilizing legs) ofthe prosthetic valve and/or implant 30, including inversion (e.g.,‘flipping’) of the implant.

For some applications of the invention, support 1040 is configured suchthat legs 910 and/or elements 900 are biased to reside in a particular(e.g., a pre-selected) configuration. For example, legs 910 and/orelements 900 and/or a coupling point (e.g., coupling point 911) maycomprise a shape-memory material (e.g., nitinol, stainless steel, nickelcobalt, cobalt chrome, and/or titanium) or a spring mechanism. For someapplications of the invention, the pre-selected configuration of legs910 comprises the stabilizing configuration of legs 910.

For some applications of the invention, legs 910 and/or elements 900 arerotatable around coupling point 911. For example, legs 910 and/orelements 900 may be coupled to upstream support portion 41 via a hingepoint (e.g., a hinge element), which may comprise a flexible materialand/or moving components. For some applications of the invention, legs910 and/or elements 900 rotate freely around coupling point 911 as faras their shape and juxtaposition allows.

For some applications where elements 900 rotate freely, following thecoupling of elements 900 to leaflets 82 of the native valve, theleaflets continue to function, at least in part.

For some applications where stabilizing legs 910 rotate freely, thestabilizing legs have (1) a floating configuration, in which thestabilizing legs rotate freely, and (2) a stabilizing configuration, inwhich the stabilizing legs assume the pre-selected configuration, andare movable from the floating configuration to the pre-selectedconfiguration. For some such applications, stabilizing legs assume thefloating configuration when support 1040 is implanted, and are moved tothe stabilizing configuration when the prosthetic valve is deployed inthe lumen of the support.

FIG. 36B shows a top (i.e., atrial side) view of implant 30, comprisingsupport 1040 and prosthetic valve 42, following implantation in nativevalve 23, comprising mitral valve 24, in accordance with someapplications of the invention. Zones (scallops) P1, P2 and P3 ofposterior leaflet 82 p, and zones A1 and A3 of anterior leaflet 82 a arelabeled. As described hereinabove, elements 900 and legs 910 aredisposed at inner edge 68 in an alternating manner. For the applicationsof the invention illustrated in FIG. 36B, elements 900 and legs 910 aretypically arranged such that (1) the two elements 900 are disposedopposite each other, (2) the two legs 910 are disposed opposite eachother, and (3) each leg 910 is generally midway between the two elements900. That is, inner edge 68 is typically elliptical (e.g., circular),and each leg 910 is disposed at edge 68 generally between 80 degrees and100 degrees (e.g., 90 degrees) to an element 900.

Typically, support-anchoring elements 900 are coupled to leaflets 82,i.e., one element 900 is coupled to anterior leaflet 82 a, and oneelement 900 is coupled to posterior leaflet 82 p. Typically, stabilizinglegs 910 are oriented toward zones (scallops) P1 and P3 of the posteriorleaflet. This configuration and orientation of elements 900 and legs 910with respect to each other, and with respect to the native valve, ishypothesized to facilitate the stable placement and coupling (i.e.,implantation) of prosthetic valve support 1040 at/to the native valve,and thereby is hypothesized to facilitate the stable implantation ofimplant 30 at the native valve.

FIG. 36C shows a top (i.e., atrial side) view of implant 30, comprisingsupport 1040 and prosthetic valve 42, following implantation in nativevalve 23, comprising mitral valve 24, in accordance with someapplications of the invention. Zones (scallops) P1, P2 and P3 ofposterior leaflet 82 p, and zones A1 and A3 of anterior leaflet 82 a arelabeled. As described hereinabove, elements 900 and legs 910 aredisposed at inner edge 68 in an alternating manner. For the applicationsof the invention illustrated in FIG. 36C, support-anchoring elements 900are coupled to leaflets 82, i.e., one element 900 is coupled to anteriorleaflet 82 a, and one element 900 is coupled to posterior leaflet 82 p.Elements 900 and legs 910 are typically arranged such that (1) the twoelements 900 are disposed opposite each other, and (2) each leg 910 isdisposed between 30 degrees and 120 degrees (e.g., between 60 degreesand 120 degrees) from the element 900 that is coupled to the posteriorleaflet.

Stabilizing legs 910 are thereby typically oriented toward parts ofposterior leaflet 82 p. This configuration and orientation of elements900 and legs 910 with respect to each other, and with respect to thenative valve, is hypothesized to facilitate the stable placement andcoupling (i.e., implantation) of prosthetic valve support 1040 at/to thenative valve, and thereby is hypothesized to facilitate the stableimplantation of implant 30 at the native valve.

FIG. 36D shows a top (i.e., atrial side) view of implant 30, comprisingsupport 1040 and prosthetic valve 42, following implantation in nativevalve 23, comprising mitral valve 24, in accordance with someapplications of the invention. Zones (scallops) P1, P2 and P3 ofposterior leaflet 82 p, and zones A1 and A3 of anterior leaflet 82 a arelabeled. As described hereinabove, elements 900 and legs 910 aredisposed at inner edge 68 in an alternating manner. For the applicationsof the invention illustrated in FIG. 36D, support-anchoring elements 900are coupled to leaflets 82, i.e., one element 900 is coupled to anteriorleaflet 82 a, and one element 900 is coupled to posterior leaflet 82 p.Elements 900 and legs 910 are typically arranged such that (1) the twoelements 900 are disposed opposite each other, and (2) each leg 910 isdisposed between 30 degrees and 120 degrees (e.g., between 60 degreesand 120 degrees) from the element 900 that is coupled to the anteriorleaflet.

Stabilizing legs 910 are thereby typically oriented toward parts ofanterior leaflet 82 a. This configuration and orientation of elements900 and legs 910 with respect to each other, and with respect to thenative valve, is hypothesized to facilitate the stable placement andcoupling (i.e., implantation) of prosthetic valve support 1040 at/to thenative valve, and thereby is hypothesized to facilitate the stableimplantation of implant 30 at the native valve.

Reference is made to FIGS. 37A-H, which are schematic illustrations ofprosthetic valve support 1040, comprising a prosthetic valve support1040 a, and the implantation thereof in a native valve, in accordancewith some applications of the invention. For some applications of theinvention, support 1040 a is an embodiment of prosthetic valve support40, described hereinabove. FIG. 37A shows a lower side view, and somedetailed views, of support 1040 a. Support 1040 a comprises twosupport-anchoring elements 900, comprising support-anchoring elements900 a, and two stabilizing legs 910. Typically, elements 900 a and legs910 are disposed at inner edge 68 such that (1) the two elements 900 aare disposed opposite each other, (2) the two legs 910 are disposedopposite each other, and (3) each leg 910 is generally midway betweenthe two elements 900 a. That is, inner edge 68 is typically elliptical(e.g., circular), and each leg 910 is disposed at edge 68 generally at aright angle (e.g., between 80 degrees and 100 degrees, such as 90degrees) to an element 900 a.

Support-anchoring element 900 a comprises two clip elements, such asplate 920 and plate 922, (1) coupled at a coupling point, and (2)between which, during implantation, leaflets 82 of the native valve areclamped. Typically, plate 920 is substantially immobile, and plate 922is (1) biased to assume a first configuration, and (2) movable betweenthe first configuration and another configuration. Typically, the firstconfiguration of plate 922 is a closed configuration. Typically, theother configuration of plate 922 is an open configuration, whereby aportion of plate 922 that is furthest from the coupling point isdisposed (1) further from plate 920 than is the same portion in thefirst, closed configuration, and (2) further from plate 920 than aportion of plate 922 that is closest to the coupling point. When plate922 is in the closed configuration thereof, element 900 a is in a closedconfiguration thereof. When plate 922 is in the open configurationthereof, element 900 a is in an open configuration thereof. That is,element 900 a is movable between open and closed configurations thereof,by plate 922 moving between open and closed configurations thereof. FIG.37A shows detailed illustrations of support-anchoring element 900 a inthe open and closed configurations, and further shows an exploded viewof the components of element 900 a.

Support-anchoring element 900 a further comprises, or is coupled to, anactuator, typically comprising a pull-wire 924, which facilitatesmovement of plate 922 between the closed and open configurations.Pull-wire 924 is typically coupled to plate 922, and controlled fromoutside the subject. For example, pull-wire 924 may be coupled to plate922, and extend to a control unit outside the body of the subject, foruse by a physician. Typically, pull-wire 924 is coupled to the portionof plate 922 that is furthest from the coupling point, such thatmovement of the pull-wire proximally (e.g., by pulling) moves plate 922toward the open configuration. For some applications of the invention,pull-wire 924 is slidably coupled to another part of element 900 a, suchas plate 920, and/or to another part of support 1040 a, and/or to a partof delivery apparatus, such as core 926, as shown in FIGS. 37C-E. Thatis, plate 922, and thereby element 900 a, are configured to be biasedtoward assuming a closed configuration, such that the user (1) activelyopens element 900 a to envelop a leaflet 82, and (2) releases element900 a to couple the element to the leaflet (i.e., to clamp the leafletbetween plates 920 and 922).

For some applications of the invention, both support-coupling elements900 a are controlled simultaneously by a user (e.g., support-couplingelements 900 a are configured to operate simultaneously). For someapplications, each element 900 a is controllable independently. For someapplications, element 900 a further comprises one or more grips, such asteeth 928, which facilitate the clamping of leaflets 82 when element 900a is closed.

FIG. 37B shows a top side view of prosthetic valve support 1040 a.Support-coupling elements 900 a are shown in their closed configuration.

FIG. 37C shows prosthetic valve support 1040 a being delivered to nativevalve 23, comprising mitral valve 24. Support 1040 a is shown in apartially deployed configuration, whereby upstream support portion 41 iscompressed within an overtube 1044, and support-anchoring elements 900 aand stabilizing legs 910 are exposed from the distal end of theovertube. Support-anchoring elements 900 a are shown in the closedconfiguration thereof. Typically, prior to deployment, at least part ofsupport 1040 a is coupled to (e.g., disposed around) a scaffold, such asa core 926. For some applications of the invention, core 926 isconfigured to facilitate the opening of elements 900 a (i.e., movementof elements 900 a and/or plate 922 to the open configuration), and/or tofacilitate the enveloping of leaflets 82 of the native valve by elements900 a. For example, and as shown in FIG. 37C, core 926 may supportelements 900 a at an angle that facilitates the movement of plate 922 bypull-wire 924.

FIG. 37D shows, in cross-section, support 1040 a in a partially-deployedconfiguration within native valve 23. Upstream support portion 41 ofsupport 1040 a is in a compressed configuration thereof, and ispartially disposed within overtube 1044. Support-anchoring elements 900a and stabilizing legs 910 are exposed from the distal end of theovertube (i.e., have been deployed from the overtube). Arrows indicatethe movement of pull-wire 924, caused by proximally pulling thepull-wire. Support-anchoring elements 900 a are shown having been movedto the open configuration thereof, by the movement of pull-wire 924. Apart of each leaflet 82 is shown within the ‘clip’ of a respectiveelement 900 a (i.e., enveloped by and/or disposed between plate 920 andplate 922 of a respective element 900 a). For some applications, theentry of leaflets 82 between the plates is facilitated by the movementof the leaflets caused by the beating of heart 22. For someapplications, the entry of leaflets 82 between the plates is facilitatedby movement of support 1040 a, and/or iterative opening and closing ofelements 900 a.

FIG. 37E shows support-anchoring elements 900 a having moved to theclosed configuration thereof, following the release of pull-wire 924.Arrows indicate the movement of pull-wire 924 following the releasethereof. The part of each leaflet 82 that was previously disposedbetween plate 920 and plate 922 is thereby clamped between the twoplates. That is, elements 900 a are coupled to leaflets 82 of the nativevalve. Once elements 900 a have been successfully coupled to leaflets 82(e.g., once a physician is satisfied with the position and coupling ofsupport 1040 a), the remainder of the support (e.g., upstream supportportion 41) is typically deployed.

FIG. 37F shows prosthetic valve support 1040 a in a fully-deployedconfiguration thereof. Following coupling of elements 900 a to leaflets82, overtube 1044 is retracted proximally, and/or support 1040 a ismoved distally, such that the support emerges from the overtube, andexpands to its expanded configuration. For some applications, theexpansion of support 1040 a automatically decouples the support from thescaffold (e.g., core 926), which is subsequently removed from thesubject. Annular portion 41 of support 1040 a is shown disposed againstthe proximal side (e.g., the atrial surface) of the native valve, asdescribed hereinabove with respect to upstream support portion 41 ofother prosthetic valve supports. FIG. 37D shows native valve 23 in anopen configuration thereof, whereby leaflets 82 generally extend intoventricle 28. As described hereinabove, mutatis mutandis, with referenceto elements 900, illustrated in FIGS. 36A-D, for some applications,elements 900 a are configured to allow leaflets 82 to continue tofunction, at least in part. For such applications, FIG. 37F illustratesa snapshot of the position of leaflets 82 during diastole. As alsodescribed hereinabove, mutatis mutandis, with reference to elements 900,illustrated in FIGS. 36A-D, for some applications, elements 900 a areconfigured to be biased to assume a pre-selected position with respectto upstream support portion 41. For such applications, FIG. 37Fillustrates leaflets 82 being held in the open configuration thereof, byelements 900 a that are configured to be biased to assume the positionshown.

For some applications, following deployment of support 1040 a, pull-wire924, or a portion thereof, is decoupled from the support, or a portionthereof, (e.g., from element 900 a). For example, the pull-wire may becoupled to element 900 a using a lock described herein (e.g., withreference to FIGS. 45A-C and/or 64A-C, mutatis mutandis), and decoupledfrom element 900 a by moving the lock to the open configuration.Alternatively, the pull-wire may be coupled to element 900 a by beinglooped around the element, and decoupled from the element by beingunlooped from the element, e.g., by subsequent to a portion of thepull-wire being cut and/or released.

FIG. 37G shows prosthetic valve 42, having been deployed (e.g.,delivered and expanded) in the lumen of prosthetic valve support 1040 a,and coupled thereto, as described herein (e.g., with reference to otherprosthetic valve supports).

FIG. 37H is a top (e.g., atrial) view of prosthetic valve 42, havingbeen deployed (e.g., delivered and expanded) in the lumen of prostheticvalve support 1040 a, and coupled thereto, as described herein (e.g.,with reference to other prosthetic valve supports). Support-anchoringelements 900 a are coupled to leaflets 82, i.e., one element 900 a iscoupled to anterior leaflet 82 a, and one element 900 a is coupled toposterior leaflet 82 p. Elements 900 a and legs 910 are typicallyarranged such that (1) the two elements 900 a are disposed opposite eachother, and (2) each leg 910 is disposed between 60 degrees and 120degrees from the element 900 a that is coupled to the posterior leaflet.

Reference is made to FIGS. 38A-H, which are schematic illustrations ofprosthetic valve support 1040, comprising a prosthetic valve support1040 b, and the implantation thereof in a native valve, in accordancewith some applications of the invention. For some applications of theinvention, support 1040 b is an embodiment of prosthetic valve support40, described hereinabove. FIG. 38A shows a lower side view, and somedetailed views, of support 1040 b. Support 1040 b comprises twosupport-anchoring elements 900, comprising support-anchoring elements900 b, and two stabilizing legs 910. Typically, elements 900 b and legs910 are disposed at inner edge 68 such that (1) the two elements 900 bare disposed opposite each other, (2) the two legs 910 are disposedopposite each other, and (3) each leg 910 is generally midway betweenthe two elements 900 b.

Support-anchoring element 900 b comprises two clip elements, such asplate 940 and plate 942, (1) coupled at a coupling point, and (2)between which, during implantation, leaflets 82 of the native valve areclamped. Typically, plate 940 is substantially immobile, and plate 942is (1) biased to assume a first configuration, and (2) movable betweenthe first configuration and another configuration. Typically, the firstconfiguration of plate 942 is an open configuration, whereby a portionof plate 942 that is furthest from the coupling point is disposedfurther from plate 940 than a portion of plate 942 that is closest tothe coupling point. Typically, the other configuration of plate 942 is aclosed configuration, whereby a portion of plate 942 that is furthestfrom the coupling point is disposed closer to plate 940 than is the sameportion in the first, open configuration. When plate 942 is in theclosed configuration thereof, element 900 b is in a closed configurationthereof. When plate 942 is in the open configuration thereof, element900 b is in an open configuration thereof. That is, element 900 b ismovable between open and closed configurations thereof, by plate 942moving between open and closed configurations thereof.

FIG. 38A shows detailed illustrations of support-anchoring element 900 bin the open and closed configurations, and further shows an explodedview of the components of element 900 b. As shown in the exploded view,for some applications, plate 942 comprises more than one element,including a spring element 942 a, and a face element 942 b. Springelement 942 a typically comprises a strip of shape-memory material(e.g., nitinol, stainless steel, nickel cobalt, cobalt chrome, and/ortitanium), that is configured such that plate 942 is biased to assumethe open configuration. Spring element 942 a is typically configured toprovide a force that is (1) sufficiently strong to provide this bias,but (2) sufficiently weak so as to facilitate (e.g., to not inhibit)sliding of cuff 944 over plate 942. Typically, this configuration isprovided by selecting an appropriate thickness of the strip ofshape-memory material of spring element 942 a. Face element 942 b istypically configured to increase the rigidity of at least part of plate942, thereby facilitating clamping of the native leaflets when cuff 944is slid over plate 942.

Support-anchoring element 900 b further comprises an actuator, typicallycomprising a restraint, such as cuff 944, which facilitates movement ofplate 922 between the closed and open configurations. Cuff 944 istypically coupled to plate 940 and/or plate 942, and controlled fromoutside the subject (e.g., controlled from outside the body of thesubject by a physician, such as via a control unit). Typically, cuff 944is coupled to plate 940 via a spring 950, and is slidable over (e.g.,onto and off of) at least a portion of plate 942. Support-anchoringelement 900 b is configured such that (1) spring 950 applies a force(i.e., a first force) to cuff 944, that slides cuff 944 over plate 942,and (2) sliding of cuff 944 over plate 942 moves the portion of plate942 that is furthest from the coupling point closer to plate 940 (i.e.,moves plate 942, and thereby element 900 b, into the closedconfiguration). A user typically opens element 900 b (e.g., so as toclamp leaflets of the native valve, e.g., as described hereinbelow withreference to FIGS. 38D-E) by sliding cuff 944 off of plate 942. Forexample, a control rod 952 may be used to slide cuff 944 off of plate942 (e.g., by distal movement of the control rod), and may becontrolled, by a physician, via a control unit outside the body of thesubject. That is, (1) plate 942 itself is configured to be biased towardassuming an open configuration, (2) cuff 944 and spring 950 areconfigured to move plate 942 toward a closed configuration, and (3) theuser (a) actively opens element 900 b by sliding cuff 944 off of plate942, so as to envelop a leaflet 82, and (b) releases cuff 944 to couplethe element to the leaflet (i.e., to clamp the leaflet between plates940 and 942).

For some applications of the invention, both support-coupling elements900 b are controlled simultaneously by a user (e.g., support-couplingelements 900 b are configured to operate simultaneously). For someapplications, each element 900 b is controllable independently. For someapplications, element 900 b further comprises one or more grips, such asteeth 948, which facilitate the clamping of leaflets 82 when element 900b is closed. For some applications, control rod 952 is moved distallyusing a pusher (not shown), disposed within delivery apparatus (e.g.,overtube 1044), and typically not fixedly coupled to the control rod.

FIG. 38B shows a top side view of prosthetic valve support 1040 b.Support-coupling elements 900 b are shown in their open configuration.

FIG. 38C shows prosthetic valve support 1040 b being delivered to nativevalve 23, comprising mitral valve 24. Support 1040 b is shown in apartially deployed configuration, whereby upstream support portion 41 iscompressed within overtube 1044, and support-anchoring elements 900 band stabilizing legs 910 are exposed from the distal end of theovertube. Support-anchoring elements 900 b are shown in the closedconfiguration thereof. Typically, prior to deployment, at least part ofsupport 1040 b is coupled to (e.g., disposed around) a scaffold, such asa core 946. For some applications of the invention, core 946 isconfigured to facilitate the opening of elements 900 b (i.e., movementof elements 900 b and/or plate 942 to the open configuration), and/or tofacilitate the enveloping of leaflets 82 of the native valve by elements900 b. For example, and as shown in FIG. 38C, core 946 may supportelements 900 b at a pre-selected angle.

FIG. 38D shows support 1040 b in a partially-deployed configurationwithin native valve 23. Annular portion 41 of support 1040 b is in acompressed configuration thereof, and is partially disposed withinovertube 1044. Support-anchoring elements 900 b and stabilizing legs 910are exposed from the distal end of the overtube (i.e., have beendeployed from the overtube). Arrows indicate the movement of cuff 944,caused by distal movement (e.g., pushing) of control rod 952.Support-anchoring elements 900 b are shown having been moved to the openconfiguration thereof, by the movement of cuff 944. A part of eachleaflet 82 is shown within the ‘clip’ of a respective element 900 b(i.e., enveloped by and/or disposed between plate 940 and plate 942 of arespective element 900 b). For some applications, the entry of leaflets82 between the plates is facilitated by the movement of the leafletscaused by the beating of heart 22. For some applications, the entry ofleaflets 82 between the plates is facilitated by movement of support1040 b, and/or iterative opening and closing of elements 900 b.

FIG. 38E shows support-anchoring elements 900 b having moved to theclosed configuration thereof, following the release of cuff 944 (e.g.,caused by the release of control rod 952). Arrows indicate the movementof cuff 944 following the release thereof. The part of each leaflet 82that was previously enveloped by (i.e., disposed between) plate 940 andplate 942 is thereby clamped between the two plates. That is, elements900 b are coupled to leaflets 82 of the native valve. Once elements 900b have been successfully coupled to leaflets 82 (e.g., once a physicianis satisfied with the position and coupling of support 1040 b), theremainder of prosthetic valve support 1040 b (e.g., upstream supportportion 41) is typically deployed.

FIG. 38F shows prosthetic valve support 1040 b in a fully-deployedconfiguration thereof. Following coupling of elements 900 b to leaflets82, overtube 1044 is retracted proximally, and/or support 1040 b ismoved distally, such that the support emerges from the overtube, andexpands to its expanded configuration. For some applications, theexpansion of support 1040 b automatically decouples the support from thescaffold (e.g., core 946), which is subsequently removed from thesubject. Annular portion 41 of support 1040 b is shown disposed againstthe proximal side (e.g., the atrial surface) of the native valve, asdescribed hereinabove with respect to upstream support portion 41 ofother prosthetic valve supports. FIG. 38D shows native valve 23 in anopen configuration thereof, whereby leaflets 82 generally extend intoventricle 28. As described hereinabove, mutatis mutandis, with referenceto elements 900, illustrated in FIGS. 36A-D, for some applications,elements 900 b are configured to allow leaflets 82 to continue tofunction, at least in part. For such applications, FIG. 38F illustratesa snapshot of the position of leaflets 82 during diastole. As alsodescribed hereinabove, mutatis mutandis, with reference to elements 900,illustrated in FIGS. 36A-D, for some applications, elements 900 b areconfigured to be biased to assume a pre-selected position with respectto upstream support portion 41. For such applications, FIG. 38Fillustrates leaflets 82 being held in the open configuration thereof, byelements 900 b that are configured to be biased to assume the positionshown.

As described hereinabove, for some applications, control rod 952 ismoved distally using a pusher, disposed within delivery apparatus (e.g.,overtube 1044), and typically not fixedly coupled to the control rod.For such applications, the pusher remains within the delivery apparatus,and is removed with the delivery apparatus, following full deployment ofprosthetic valve support 1040 b. FIG. 38F thus shows a proximal end 953of each control rod 952, previously disposed within overtube 1044, nowexposed and not in contact with the pusher, following removal of theovertube.

FIG. 38G shows prosthetic valve 42, having been deployed (e.g.,delivered and expanded) in the lumen of prosthetic valve support 1040 b,and coupled thereto, as described herein (e.g., with reference to otherprosthetic valve supports).

FIG. 38H is a top (e.g., atrial) view of prosthetic valve 42, havingbeen deployed (e.g., delivered and expanded) in the lumen of prostheticvalve support 1040 b, and coupled thereto, as described herein (e.g.,with reference to other prosthetic valve supports). Support-anchoringelements 900 b are coupled to leaflets 82, i.e., one element 900 b iscoupled to anterior leaflet 82 a, and one element 900 b is coupled toposterior leaflet 82 p. Elements 900 b and legs 910 are typicallyarranged such that (1) the two elements 900 b are disposed opposite eachother, and (2) each leg 910 is disposed between 60 degrees and 120degrees from the element 900 b that is coupled to the posterior leaflet.

Reference is again made to FIGS. 36A-38H. Typically, support-anchoringelements 900 (e.g., elements 900 a and 900 b) and stabilizing legs 910are configured to be movable independently from each other, and to be atleast in part flexible and/or movable with respect to upstream supportportion 41. That is, elements 900 and legs 910 are typicallypositionable according to the individual anatomy of the subject in whichthe implant is implanted. For some applications of the invention, thisis conferred at least in part by the connection between (1) the element900 and/or leg 910, and (2) upstream support portion 41. For someapplications of the invention, this is conferred at least in part by thecomposition of the element 900 and/or leg 910 itself. For example, forsome applications, techniques and/or elements described with referenceto FIGS. 2-7 and 17A-20F, may be used in combination with thosedescribed with reference to FIGS. 36A-37H (e.g., in combination withsupport-anchoring elements 900, 900 a, and/or 900 b, and stabilizinglegs 910).

For some applications of the invention, during the deployment (e.g.,implantation) of prosthetic valve support 1040 (e.g., support 1040 a,and/or support 1040 b), the user (e.g., physician) may determine thequality (e.g., strength) of coupling of support-anchoring elements 900(e.g., elements 900 a, and/or 900 b) by applying a force (e.g., pushing,pulling, twisting) to the device, and/or using imaging techniques tovisualize the device in situ.

Typically, support-anchoring elements 900 (e.g., elements 900 a and/or900 b) are operable (i.e., openable, and/or closable) repeatedly. Shouldcoupling of elements 900 to leaflets 82 be determined to be suboptimal,elements 900 may be opened (e.g., decoupled from the leaflets) andreclosed (e.g., re-coupled to the leaflets), until optimal coupling hasbeen achieved.

Should it be necessary and/or desirable during deployment, untilprosthetic valve support 1040 (e.g., support 1040 a, and/or support 1040b) is fully deployed (e.g., from overtube 1044), the deployed, expandedportions of the support (i.e., the portions of the support, includingelements 900) that are exposed from the overtube may be drawn back intothe overtube (e.g., for repositioning, or for withdrawal from the bodyof the subject).

It is to be noted that, although the support-anchoring elementsdescribed with reference to FIGS. 36A-38H (e.g., elements 900, 900 a and900 b) are described and/or illustrated in the context of prostheticvalve supports that comprise two support-anchoring elements and twostabilizing legs (e.g., as described with reference to FIGS. 36A-D), thescope of the invention includes other contexts for thesesupport-anchoring elements, and the clip functionality thereof. Forexample, for some applications of the invention, a prosthetic valvesupport comprises two support-anchoring elements 900 a and/orsupport-anchoring elements 900 b, and does not comprise stabilizing legs910. For some applications of the invention, a prosthetic valve supportcomprises greater or fewer than two such support-anchoring elements.Furthermore, for some applications of the invention, the structureand/or function of element 900 a and/or 900 may be incorporated in avalve-anchoring element (e.g., valve-anchoring element 64). That is, forsome applications of the invention, a prosthetic valve comprises atleast one valve-anchoring element, which is described as asupport-anchoring element with reference to one or more of FIGS.36A-38H, mutatis mutandis.

Reference is made to FIGS. 39A-D, which are schematic illustrations of amedical device 150, comprising one or more coupling tabs 1100, inaccordance with some applications of the invention. Coupling tabs 1100facilitate delivery of medical device 150, by facilitating reversiblecoupling of the medical device to a delivery apparatus, such as, but notlimited to, delivery apparatus 880 (described with reference to FIGS.27A-D). FIGS. 39A-D illustrate medical device 150 as comprisingprosthetic valve 42. However, it should be noted that the scope of theinvention includes coupling tabs 1100 that facilitate delivery of othermedical devices (e.g., expandable medical devices). FIGS. 39A-B showcoupling tabs 1100 comprising T-shaped coupling tabs 1100 a, and FIG.39C-D show coupling tabs 1100 comprising box-shaped coupling tabs 1100b. Tabs 1100 a and 1100 b are configured, respectively, to be reversiblycouplable to delivery apparatus of a respective, complimentaryconfiguration.

As described hereinabove, prosthetic valve 42 has (1) a compressedconfiguration, in which it is typically delivered, within a deliverytube (e.g., tube 60), to the implantation site (e.g., native valve 23),and (2) an expanded configuration, toward which the prosthetic valvemoves during deployment. Coupling tabs 1100 are configured such that (1)in the compressed configuration of the prosthetic valve, the tabs assumea restrained configuration (FIGS. 39A and 39C), and (2) in the expandedconfiguration of the prosthetic valve, the tabs assume an unconstrainedconfiguration, e.g., a pre-selected configuration (FIGS. 39B and 39D).Typically, in the restrained configuration, coupling tabs 1100 extendcollinearly from an end of prosthetic valve 42. For example, and asillustrated in FIGS. 39A and 39C, coupling tabs 1100 extend proximallyfrom the proximal end of the prosthetic valve. Typically, in theunconstrained configuration, at least part of each coupling tab 1100protrudes radially from primary structural element 130 of the prostheticvalve. For some applications, and as illustrated in FIGS. 39B and 39D,in the unconstrained configuration, coupling tabs 1100 extend radiallyoutward from primary structural element 130 of the prosthetic valve. Thearrows indicate the direction of the movement of coupling tabs 1100 fromthe constrained to the unconstrained configuration. This movement istypically between 5 degrees and 180 degrees (e.g., between 80 degreesand 180 degrees). For some applications, this movement is greater than180 degrees, whereby coupling tabs 1100 protrude into voids defined byprosthetic valve 42.

Typically, coupling tabs 1100 comprise a shape-memory material (e.g.,nitinol, stainless steel, nickel cobalt, cobalt chrome, and/ortitanium), and the unconstrained configuration is pre-selected byshape-setting the material.

It is hypothesized that, when prosthetic valve 42 is implanted in thenative valve, coupling tabs 1100 (e.g., tabs 1100 a and tabs 1100 b),advantageously, disturb blood flow less than some coupling tabs that donot move into a configuration in which at least part of the tabsprotrude radially from the prosthetic valve. For example, for someapplications, coupling tabs 1100 protrude less far proximally into theatrium from the proximal part of primary structural element 130, and/orare disposed further peripherally to a flow of blood through theprosthetic valve. It is hypothesized that this reduced blood flowdisturbance of tabs 1100 reduces the likelihood of inducing hemodynamicdisorders such as thrombus formation. It is further hypothesized thatthis reduced proximal protrusion into the atrium, increases theavailable space in the atrium, thereby facilitating the delivery,removal and/or other movement of medical devices and/or deliveryapparatus in the vicinity of the prosthetic valve.

For some applications of the invention, coupling tabs 1100 (e.g.,coupling tabs 1100 a, and/or coupling tabs 1100 b) further facilitatecoupling of the prosthetic valve to the prosthetic valve support (e.g.,prosthetic valve support 40). As described herein, the size of the lumenof support 40 typically determines the size to which prosthetic valve 42expands, when implanted in this lumen. Thus, when implanted and expandedin the lumen of prosthetic valve support 40, the primary structuralelement of prosthetic valve 42 typically has a longest transversecross-sectional length that generally corresponds to a longesttransverse cross-sectional length of the lumen of support 40. Atransverse cross section of prosthetic valve 42 at the position ofradially-protruding coupling tabs 1100, typically has a longest lengththat is greater than the longest transverse cross-sectional length ofthe lumen of support 40. That is, in the region of coupling tabs 1100,prosthetic valve 42 is typically wider than in other (e.g., more distal)regions of the prosthetic valve. This extra width provides axialresistance against undesired distal (e.g., ventricular) movement ofprosthetic valve 42 with respect to support 40, in addition to theresistance typically provided by radially expansive forces of prostheticvalve against the support.

For some applications of the invention, coupling tabs 1100 (e.g.,coupling tabs 1100 a, and/or coupling tabs 1100 b) increase the rigidityof prosthetic valve 42 (e.g., the rigidity of primary structural element130 of the prosthetic valve). For example, for some applications, whenprimary structural element 130 is generally cylindrical, coupling tabs1100 inhibit deformation of element 130.

Reference is made to FIGS. 40A-C, which are schematic illustrations ofprosthetic valve 42, comprising prosthetic valve 2000, which comprisesone or more tissue-engaging elements 2002. For some applications,elements 2002 are embodiments of tissue-engaging elements 62. For someapplications, elements 2002 are embodiments of valve-anchoring elements64. Tissue-engaging elements 2002 protrude laterally from primarystructural element 130 of prosthetic valve 2000.

Tissue-engaging elements 2002 are configured to couple to leaflets 82 ofthe native valve, subsequent to the deployment (e.g., implantation) ofprosthetic valve 2000. Typically, elements 2002 are configured to coupleto the leaflets by piercing the leaflets, at least in part.

For some applications, prosthetic valve 2000 comprises two elements2002, that are disposed at sites on the circumference of primarystructural element 130 that are generally opposite each other. For someapplications of the invention, prosthetic valve 2000 comprises more thantwo (e.g., four or more, such as six or more) elements 2002, that aredisposed circumferentially around primary structural element 130.

For some applications, tissue-engaging elements 2002 protrude generallyorthogonally to the outer surface of primary structural element 130(i.e., generally straight outward laterally from element 130). For someapplications, elements 2002 protrude at an acute angle from the outersurface of primary structural element 130. For example, and asillustrated in FIGS. 40A-C, elements 2002 may protrude proximally, suchthat a portion (e.g., a tip) of elements 2002 that is further from apoint of coupling between the element 2002 and primary structuralelement 130, is closer to the proximal end of element 130 than is aportion of elements 2002 that is closer to that point of coupling.

FIG. 40A shows prosthetic valve 2010, comprising a plurality oftissue-engaging elements 2012. Prosthetic valve 2010 is an embodiment ofprosthetic valve 2000, and elements 2012 are embodiments oftissue-engaging elements 2002. Elements 2012 are typically configured toprotrude at an acute angle from the outer surface of primary structuralelement 130 of prosthetic valve 2010. Tip 2014 is the portion of element2012 that is furthest from a point of coupling between the element 2012and element 130. For some applications of the invention, tip 2014 issharp (e.g., pointed) so as to facilitate piercing of the nativeleaflets.

FIG. 40B shows prosthetic valve 2020, comprising a plurality oftissue-engaging elements 2022. Prosthetic valve 2020 is an embodiment ofprosthetic valve 2000, and elements 2022 are embodiments oftissue-engaging elements 2002. For some applications of the invention,prosthetic valve 2020 and elements 2022 are analogous to, and/orcomprise, prosthetic valve 2010 and elements 2012, respectively.Elements 2022 are typically configured to protrude at an acute anglefrom the outer surface of primary structural element 130 of prostheticvalve 2020. For some applications of the invention, elements 2022 areformed from a lattice structure that the prosthetic valve comprises. Forexample, a separation in the structure may allow a portion of thestructure to be moved out of the plane of the structure, therebyprotruding from element 130. Element 2022 thereby comprises theprotruding portion of the structure. Tip 2024 is the portion of element2022 that is furthest from a point of coupling between the element 2022and element 130. For some applications of the invention, tip 2024 issharp (e.g., pointed) so as to facilitate piercing of the nativeleaflets.

FIG. 40C shows implant 30, comprising prosthetic valve support 2030 andprosthetic valve 2000, following implantation thereof in native valve23. Prosthetic valve support 2030 typically comprises support-anchoringelements 2032. For some applications of the invention, prosthetic valvesupport 2030 and/or support-anchoring elements 2032 are analogous,respectively, to other prosthetic valve supports and support-anchoringelements described herein. For some applications of the invention,prosthetic valve support 2030 comprises prosthetic valve support 40.

Immediately following the implantation of support 2030 and prostheticvalve 2000, leaflets 82 of the native valve typically continue tofunction, at least in part. For example, support-anchoring elements 2032may be configured to rotate around a coupling point with upstreamsupport portion 41 of the prosthetic valve, so as to allow the leafletsto continue to function, at least in part (e.g., as described herein forseveral support-anchoring elements). When leaflets 82 move againstprosthetic valve 2000 (e.g., during systole), tissue-engaging elements2002 couple to (e.g., by piercing) the leaflets.

For some applications of the invention, tissue-engaging elements 2032are configured to move leaflets 82 against prosthetic valve 2000, andthereby onto tissue-engaging elements 2002. For example, elements 2032may be configured to move toward each other, such that followingimplantation of prosthetic valve support 2030 and coupling of elements2032 to leaflets 82, when prosthetic valve 2000 is deployed in the lumenof support 2030, elements 2032 push leaflets 82 against the prostheticvalve.

It is hypothesized that such coupling of leaflets 82 to elements 2002,and thereby to prosthetic valve 2000, facilitates (1) stableimplantation of implant 30 in the native valve, and/or (2) sealing ofleaflets 82 around the prosthetic valve, thereby inhibiting retrogradeleakage of blood between the leaflets and the implant.

FIG. 40C shows, by way of illustration and not limitation, prostheticvalve 2000 being used in combination with a prosthetic valve supportthat comprises support-anchoring elements. It is to be noted that, forsome applications, prosthetic valve 2000 is used in combination withother prosthetic valve supports that comprise support-anchoringelements, and/or with prosthetic valve supports that do not comprisesupport-anchoring elements.

Reference is made to FIGS. 41A-B, 42A-B, 43A-C, and 44A-B, which areschematic illustrations of prosthetic valves and prosthetic valvesupports, comprising a coupling functionality for couplingsupport-anchoring elements of the prosthetic valve support to theprosthetic valve.

Reference is now made to FIGS. 41A-B, which are schematic illustrationsof prosthetic valve support 40, comprising a prosthetic valve support1122, which comprises one or more support-anchoring elements 1124, inaccordance with some applications of the invention. FIG. 41A showssupport 1122, and FIG. 41B shows, implanted in a native valve 23, animplant 30, which comprises support 1122 and prosthetic valve 42,comprising a prosthetic valve 1120. For some applications of theinvention, support-anchoring elements 1124 comprise (1) othersupport-anchoring elements described herein (e.g., support-anchoringelements 66), and/or (tissue-engaging elements 62). Support-anchoringelements 1124 comprise one or more barbs 1126, which comprise thecoupling functionality for coupling the support-anchoring elements ofthe prosthetic valve support to the prosthetic valve. Typically, eachbarb 1126 protrudes from another part of element 1124 at between 10degrees and 80 degrees (e.g., between 15 degrees and 60 degrees).Typically, a tip of each barb is thereby disposed more distally (e.g.,ventricularly) than a base of that barb. Typically, each barb 1136 has alength of between 0.5 and 5 mm.

Prosthetic valve support 1122 is typically delivered to, and deployedat, native valve 23, as described herein for other prosthetic valvesupports. Support-anchoring elements 1124 are typically coupled toleaflets 82 of the native valve, as described herein for othersupport-anchoring elements. Subsequent to the deployment and coupling ofsupport 1122 to the native valve, prosthetic valve 1120 is deployed inthe lumen of the prosthetic valve support, as described herein for otherprosthetic valves. As prosthetic valve 1120 expands, barbs 1126 engageand couple to the prosthetic valve, typically by protruding into voidsdefined by the prosthetic valve. For some applications of the invention,elements 1124 are configured to assume a pre-selected configuration,such as that shown in FIG. 41A, and to restrain leaflets 82. For someapplications of the invention, elements 1124 are configured to allowleaflets 82 to continue to function, at least in part. For some suchapplications, movement of leaflets 82 and elements 1124, caused by thebeating of the heart, is hypothesized to facilitate engagement of theprosthetic valve by barbs 1126.

Typically, barbs 1126 are configured to protrude into the voids definedby prosthetic valve 1120, but to not protrude further into theprosthetic valve, e.g., into the lumen defined by the prosthetic valve.Typically, prosthetic valve 1120 comprises a wire frame, and a covering1128, which covers at least part of the inner surface of the prostheticvalve (i.e., the walls of the lumen), so as to facilitate blood flowthrough the prosthetic valve. Typically, barbs 1126 are dimensioned soas to protrude into the voids defined by the prosthetic valve, but tonot protrude into and/or through covering 1128. That is, prostheticvalve 1120 and prosthetic valve support 1122 are configured so as to becouplable to each other using barbs 1126, without the barbs contacting(and possibly damaging) covering 1128.

For some applications of the invention, and as illustrated in FIG. 41B,the prosthetic valve is coupled to prosthetic valve support only by (1)a radially-expansive force exerted by the prosthetic valve on theprosthetic valve support, and (2) barbs 1126 protruding into the voidsdefined by the prosthetic valve. For such applications of the invention,the prosthetic valve (e.g., prosthetic valve 1120) is typicallycouplable to the prosthetic valve support at a plurality of relativepositions. That is, the prosthetic valve is typically implantable in thenative valve at a plurality of depths i.e., a physician may decide onthe depth at which the prosthetic valve is implanted in the nativevalve.

Reference is now made to FIGS. 42A-B, which are schematic illustrationsof prosthetic valve support 40, comprising a prosthetic valve support1132, which comprises one or more support-anchoring elements 1134, inaccordance with some applications of the invention. FIG. 42A showssupport 1132, and FIG. 42B shows, implanted in a native valve 23, animplant 30, which comprises support 1132 and prosthetic valve 42,comprising a prosthetic valve 1130. For some applications of theinvention, support-anchoring elements 1134 comprise (1) othersupport-anchoring elements described herein (e.g., support-anchoringelements 66), and/or (2) tissue-engaging elements 62. Support-anchoringelements 1134 comprise one or more barbs 1136, which comprise thecoupling functionality for coupling the support-anchoring elements ofthe prosthetic valve support to the prosthetic valve. Typically, eachbarb 1136 protrudes from another part of element 1134 at between 10degrees and 80 degrees (e.g., between 15 degrees and 60 degrees).Typically, a tip of each barb is thereby disposed more distally (e.g.,ventricularly) than a base of that barb. Typically, each barb 1136 has alength of between 0.5 and 5 mm.

The structure, function and implantation method of prosthetic valvesupport 1132 and prosthetic valve 1130, are typically similar to thoseof prosthetic valve support 1122 and prosthetic valve 1120. However,each support-anchoring element 1134 of prosthetic valve support 1132typically comprises no more than 4 barbs 1136 (e.g., 2 barbs 1136).Prosthetic valve 1130 comprises a wire frame, and a covering 1138, whichcovers at least part of the inner surface of the prosthetic valve (i.e.,the walls of the lumen), so as to facilitate blood flow through theprosthetic valve. Typically, the inner surface of a portion (e.g., adistal portion 1139) of prosthetic valve 1130 is not covered withcovering 1138. Typically, barbs 1136 are positioned and/or configured toengage and couple distal portion 1139. That is, prosthetic valve 1130and prosthetic valve support 1132 are configured so as to be couplableto each other using barbs 1136, without the barbs contacting (andpossibly damaging) covering 1138.

Reference is now made to FIGS. 43A-C, which are schematic illustrationsof a prosthetic valve support 1142, comprising one or moresupport-anchoring elements 1144, which are couplable to a prostheticvalve 1140, in accordance with some applications of the invention. Forsome applications of the invention, prosthetic valve support 1142comprises, and/or is analogous to, another prosthetic valve supportdescribed herein (e.g., prosthetic valve support 40). For someapplications of the invention, prosthetic valve 1140 comprises, and/oris analogous to, another prosthetic valve described herein (e.g.,prosthetic valve 42).

Prosthetic valve support 1142 comprises one or more support-anchoringelements 1144, which, for some applications of the invention, comprise,and/or are analogous to, (1) other support-anchoring elements describedherein (e.g., support-anchoring elements 66), and/or (2) tissue-engagingelements 62. Support-anchoring elements 1144 comprise a coupling lead1146 (e.g., a coupling wire) and a stopper 1147, which is slidablycoupled to the coupling lead. Coupling lead 114 and stopper 1147comprise the coupling functionality for coupling the support-anchoringelements of the prosthetic valve support to the prosthetic valve. Oneend (e.g., a distal end) of coupling lead 1146 is typically coupled toelement 1144, and portion (e.g., a proximal portion) of the couplinglead is slidably coupled to prosthetic valve 1140. For some applicationsof the invention, prosthetic valve 1140 is shaped to define an eyelet(not shown), through which coupling lead is slidable.

FIG. 43A shows prosthetic valve support 1142 having been deployed (e.g.,implanted) in native valve 23, and prosthetic valve 1140 in a compressedconfiguration within delivery tube 60, prior to deployment. A couplinglead 1146 is coupled to each support-anchoring element 1144, and extendsproximally, through prosthetic valve 1140.

FIG. 43B shows prosthetic valve 1140 following deployment thereof in thelumen defined by prosthetic valve support 1142. Prosthetic valve 1140has been slid over coupling leads 1146. That is, the length of eachcoupling lead that is disposed between an element 1144 and a closestportion of the prosthetic valve, has been shortened. Each stopper 1147has been slid distally over coupling lead 1146 (e.g., using a pusher;not shown), thereby sandwiching a portion of the prosthetic valvebetween each stopper and a respective element 1144. Typically, couplinglead 1146 and stopper 1147 are configured to inhibit movement of thestopper in the opposite direction. For example, stopper 1147 maycomprise a ratchet housing (e.g., may contain a ratchet mechanism), andcoupling lead 1146 may comprise ratchet teeth. Thereby, sliding ofstopper 1147 over coupling lead 1146 facilitates coupling of theprosthetic valve to the prosthetic valve support.

For some applications of the invention, coupling leads 1146 facilitaterotational orientation of prosthetic valve 1140 with respect to support1142 during deployment of the prosthetic valve in the lumen of thesupport. For example, coupling leads 1146 may act as guidewires, alongwhich the prosthetic valve is slid during deployment thereof.

For some applications of the invention, prosthetic valve 1140 is coupledto prosthetic valve support 1142 using coupling leads 1146 and stoppers1147 (i.e., stoppers 1147 are slid distally, sandwiching the portions ofthe prosthetic valve between the stoppers and elements 1144) before theprosthetic valve is fully deployed. For example, this coupling may beperformed when the prosthetic valve is semi-deployed from delivery tube60, i.e., when a proximal portion of the prosthetic valve is stillcompressed within the delivery tube.

Coupling of prosthetic valve 1140 to elements 1144 with coupling lead1146 is hypothesized to inhibit lateral rotation (e.g., rotation aroundan atrial-ventricular axis), and/or axial movement, of the prostheticvalve, with respect to the support.

Following coupling of prosthetic valve 1140 to support-anchoringelements 1144, a proximal portion of coupling lead 1146 is typicallysubsequently removed from the subject. FIG. 43C shows a distal portionof coupling lead 1146 having been decoupled from a proximal portion ofthe coupling lead. For some applications of the invention, coupling lead1146 is cut. For some applications of the invention, the proximalportion of the coupling lead comprises a loop, which is (1) coupled tothe distal portion of the coupling lead by being looped around anelement of the distal portion of the coupling lead, and (2) decoupledfrom the distal portion of the coupling lead by being unlooped from thedistal portion of the coupling lead. For some applications, the proximalportion of the coupling lead is (1) coupled to the distal portion of theguidewire using a lock described herein (e.g., with reference to FIGS.45A-C and/or 64A-C, mutatis mutandis), and (2) decoupled from the distalportion of the coupling lead by moving the lock to the openconfiguration.

Reference is made to FIGS. 44A-B, which are schematic illustrations of(1) a prosthetic valve support 1162, comprising one or moresupport-anchoring elements 1164, and (2) a prosthetic valve 1160,comprising one or more valve-anchoring elements 1166, which arecouplable to prosthetic valve support 1162, in accordance with someapplications of the invention. Typically, valve-anchoring elements 1166are couplable to the prosthetic valve support by being couplable tosupport-anchoring elements 1164. For some applications of the invention,prosthetic valve support 1142 comprises, and/or is analogous to, anotherprosthetic valve support described herein (e.g., prosthetic valvesupport 40). For some applications of the invention, prosthetic valve1160 comprises, and/or is analogous to, another prosthetic valvedescribed herein (e.g., prosthetic valve 42). For some applications ofthe invention, support-anchoring elements 1164 comprise, and/or areanalogous to, (1) other support-anchoring elements described herein(e.g., support-anchoring elements 66), and/or (2) tissue-engagingelements 62. For some applications of the invention, valve-anchoringelements 1166 comprise, and/or are analogous to, other valve-anchoringelements described herein (e.g., valve-anchoring elements 64). For someapplications of the invention, valve-anchoring elements 1166 comprise,and/or are analogous to, support-engaging elements, such assupport-engaging elements 422.

FIG. 44A shows prosthetic valve support 1162 having been deployed (e.g.,implanted) in native valve 23, and at least part of prosthetic valve1160 in a compressed configuration within delivery tube 60, prior todeployment. Valve-anchoring elements 1166 are typically coupled to adistal portion (e.g., a distal end) of the primary structural element ofprosthetic valve 1160, and, in the compressed configuration of theprosthetic valve, elements 1166 extending distally from the prostheticvalve. Elements 1166 are shown emerging from delivery tube 60. For someapplications of the invention, valve-anchoring elements 1166 are formedfrom the regular repeating structure of the lattice that forms theprosthetic valve, e.g., as described with reference to support-engagingelements 424 (FIGS. 8A-B), mutatis mutandis.

FIG. 44B shows prosthetic valve 1160 following deployment thereof in thelumen defined by prosthetic valve support 1162. Valve-anchoring elements1166 are deployed on the distal (e.g., ventricular) side of the nativevalve, and are coupled to support-anchoring elements 1164. Typically,support-anchoring elements 1164 are configured to facilitate coupling(1) of elements 1164 to the native valve (e.g., to leaflets 82), and (2)of valve-anchoring elements 1166 to support-anchoring elements 1164.Valve-anchoring elements 1166 thereby restrict proximal movement ofprosthetic valve 1160, i.e., elements 1166 couple the prosthetic valveto support 1162, and to the native valve.

Reference is made to FIGS. 45A-C, which are schematic illustrations of alock 1170 for facilitating delivery of a medical device, in accordancewith some applications of the invention.

Reference is now made to FIG. 45A. Lock 1170 comprises a tubular member1172 and a plug 1174. Plug 1174 is dimensioned such that it isdisposable in, and slidable through (e.g., into and out of) the lumen oftubular member 1172. Plug 1174 comprises a restricting portion 1190 anda second portion 1192. Lock 1170 has a locking configuration, in which(1) at least part of restricting portion 1190 is disposed inside thelumen of tubular member 1172, and (2) a coupling lead 1180 (e.g., acoupling wire) that is coupled to the lock, is generally not decouplablefrom the lock. Lock 1170 further has an open configuration, in which (1)at least restricting portion 1190 is disposed outside the lumen oftubular member 1172, and (2) coupling lead 1180 is decouplable from thelock. Typically, at least part of plug 1174 (e.g., restricting portion1190) is dimensioned so as to fit tightly in the lumen of tubular member1172, in a manner in which an outer surface of plug 1174 (e.g., an outersurface of portion 1190) is disposed very close to an inner surface oftubular member 1172, i.e., such that little space exists between the atleast part of the plug and the tubular member. Typically, a surface ofsecond portion 1192 is disposed further from the inner surface oftubular member 1172, than is the surface of the at least part of portion1190.

For some applications of the invention, second portion 1192 is shaped todefine at least part of a trough, and the surface of the second portionthat is disposed further from the inner surface of the tubular member,comprises a surface of the trough.

FIG. 45A shows coupling lead 1180 comprising a loop, and coupled to lock1170 by at least part of the loop being disposed against second portion1192 when the lock is in the locking configuration. Restricting portion1190 inhibits axial movement of the coupling lead, and tubular member1172 inhibits lateral movement of the coupling lead (e.g., the innersurface of tubular member holds the coupling lead against second portion1192). Tubular member 172 thereby facilitates coupling of coupling lead1180 to plug 1174, and thereby to lock 1170.

As is described hereinbelow, coupling lead 1180 is typically coupled toa medical device 150 and facilitates (1) coupling of medical device 150to delivery apparatus during delivery of the medical device and (2)decoupling of medical device 150 from the delivery apparatus followingimplantation of device 150.

Reference is now made to FIG. 45B. Plug 1174 is slid distally throughtubular member 1172, such that lock 1170 is in an open configuration.Typically, plug 1174 is moved using control wire 1175. In this openconfiguration, restricting portion 1190, and typically at least part ofsecond portion 1192, are exposed from the tubular member (i.e., areoutside the lumen of the tubular member). Coupling lead 1180 is shown inFIG. 45B as being disposed against a surface of second portion 1192, byway of illustration and not limitation, as a temporary configurationprior to disengagement of coupling lead 1180 from plug 1174 (i.e.,decoupling of the coupling lead from lock 1170; disengagement ofcoupling lead 1180 is described hereinbelow).

FIG. 45C shows lock 1170 in the open configuration, and coupling lead1180 decoupled from the lock. In the open configuration of the lock,coupling lead 1180 is allowed to move away from plug 1174 (e.g., tubularmember 1172 does not restrict lateral movement of the coupling lead awayfrom second portion 1192). That is, in the open configuration of thelock, coupling lead 1180 is decouplable from the lock. Typically,coupling lead 1180 is moved away from plug 1174 by moving the formerwith respect to the latter (e.g., by applying a moving force to couplinglead 1180 and/or to plug 1174). In some applications of the invention,at least a portion of coupling lead 1180 is configured such that itautomatically moves out of the trough upon being exposed from thetubular member (i.e., when lock 1170 moves to the open configuration).For example, the coupling lead may comprise a shape-memory material suchas nitinol, stainless steel, nickel cobalt, cobalt chrome, and/ortitanium. In some applications of the invention, portions 1190 and 1192are shaped to facilitate the decoupling of coupling lead 1180 from thelock. For example, a boundary between portions 1190 and 1192 may besloped.

Reference is made to FIGS. 46A-B, which are schematic illustrations ofprosthetic valve support 40, comprising prosthetic valve support 1060,which comprises one or more support-anchoring elements, such assupport-anchoring elements 900, coupled to a stabilizing element 1062(e.g., a stabilizing strip or a stabilizing element), in accordance withsome applications of the invention. FIG. 46A shows a lower side view ofsupport 1060. As described hereinabove, the support-anchoring elementsare typically coupled to inner edge 68, which defines the lumen ofupstream support portion 41. That is, a first portion (e.g., a proximalend) of each support-anchoring element is typically coupled to inneredge 68. A second portion of each support-anchoring element is typicallycoupled to stabilizing element 1062. Typically, stabilizing element 1062comprises an annular band. Further typically, a distal portion of eachsupport-anchoring elements is coupled to the stabilizing element.Stabilizing element 1062 defines an opening (e.g., an aperture), and istypically inelastic and at least partly flexible. Non-limiting examplesof materials that stabilizing element 1062 may comprise includepolyester, PTFE (e.g., ePTFE), nylon, cotton, nitinol, stainless steel,nickel cobalt, cobalt chrome, titanium, tantalum and palladium. Theflexibility of element 1062 typically facilitates the compressibility ofthe prosthetic valve support (e.g., for transvascular delivery). Forsome applications of the invention, the support-anchoring elements areconfigured to rotate freely around the point at which they couple toupstream support portion 41, e.g., so as to allow leaflets of the nativevalve to continue to function (i.e., to move), at least in part. Forsome such applications, the flexibility of stabilizing element 1062typically allows (i.e., does not generally inhibit) this movement of thesupport-anchoring elements and the leaflets.

Stabilizing element 1062 is hypothesized to increase the stability ofprosthetic valve support 1060 at the native valve. For example,stabilizing element 1062 is hypothesized to at least partly inhibitlateral rotation (e.g., rotation around an atrial-ventricular axis,e.g., ‘yaw’) of the support and/or support-anchoring elements. Followingdeployment (e.g., implantation) of the prosthetic valve, stabilizingelement 1062 is further hypothesized to reduce rolling movement (e.g.,movement around a lateral axis, e.g., an axis between two elements 900,e.g., ‘pitch’ and ‘roll’) of the prosthetic valve and/or implant 30,including inversion (e.g., ‘flipping’) of the implant.

For some applications of the invention, stabilizing element 1062 isfurther hypothesized to stabilize elements 900 during deployment of theelements, e.g., by facilitating coupling thereof to delivery apparatus.

FIG. 46B shows implant 30, comprising prosthetic valve support 1060 andprosthetic valve 42, following implantation in native valve 23. Theprosthetic valve support and the prosthetic valve are typicallyimplanted as described hereinabove, mutatis mutandis. Prosthetic valve42 is deployed (e.g., delivered and expanded) in the lumen of support1060, and in the opening defined by stabilizing element 1062. That is,when prosthetic valve 42 is deployed at the native valve, it is expandedsuch that (1) a proximal portion of the prosthetic valve couples toinner edge 68 of support 1060, and (2) a distal portion of theprosthetic valve is disposed within the opening of the stabilizingelement. For some applications of the invention, and as illustrated inFIG. 46B, the distal portion of the prosthetic valve makes contact withthe stabilizing element.

For some applications of the invention, stabilizing element 1062 isconfigured (e.g., dimensioned) such that, when the prosthetic valve isexpanded within the opening of the stabilizing element, the stabilizingelement limits the expansion of the distal portion of primary structuralelement 130 of the prosthetic valve. That is, for some applications, thecross-sectional area defined by the primary structural element 130 ofthe prosthetic valve, upon expansion of the prosthetic valve, isdetermined by the cross-sectional area of the opening of the stabilizingelement. For some applications, the cross-sectional area of the openingof the stabilizing element is substantially equal to the cross-sectionalarea of the lumen defined by upstream support portion 41, thereby theexpansion of both the distal and proximal portions of the primarystructural element are limited to the same diameter, therebyfacilitating the primary structural element to assume a cylindricalshape.

For applications where stabilizing element 1062 limits the expansion ofprosthetic valve 42, a radially-expansive force is thereby applied byprosthetic valve 42 to stabilizing element 1062. The radially-expansiveforce typically couples the prosthetic valve to the stabilizing element.That is, for some applications, prosthetic valve 42 is couplable to thestabilizing element. For some applications, the prosthetic valve iscoupled to the stabilizing element by alternative or additional means.For example, the stabilizing element may comprise barbs and/or hooks,which facilitate coupling to the prosthetic valve.

For some applications of the invention, at least part (e.g., an innersurface) of stabilizing element 1062 comprises a friction coating, thatis configured to increase friction, and thereby coupling, between thestabilizing element and the prosthetic valve.

For some applications of the invention, at least part of stabilizingelement 1062 is shaped to define ridges, which are configured (e.g.,dimensioned) to protrude between struts of the lattice structure of theprosthetic valve (i.e., into voids defined by the lattice structure).The protruding parts facilitate coupling of the stabilizing element tothe prosthetic valve, e.g., by inhibiting axial movement of theprosthetic valve through the opening defined by the stabilizing element.

For some applications of the invention, a soft (e.g., crushable)material is disposed on the inner surface of stabilizing element 1062(e.g., the stabilizing element comprises the soft material). Whenprosthetic valve 42 expands, and applies radially-expansive force to thestabilizing element, (1) the struts of the lattice structure of theprosthetic valve compress (e.g., crush) the parts of the soft materialagainst which the struts apply the force, and (2) the parts of the softmaterial that are disposed between the struts (i.e., that are disposedat voids defined by the lattice structure), form ridges that protrudebetween the struts (i.e., protrude into the voids). The protruding partsof the soft material facilitate coupling of the stabilizing element tothe prosthetic valve, e.g., by inhibiting axial movement of theprosthetic valve through the opening defined by the band, such as byincreasing friction.

For some applications of the invention, prosthetic valve 42 (e.g., theprimary structural element of prosthetic valve 42) is shaped to define acircumferential groove that is configured (e.g., dimensioned) to receivestabilizing element 1062. That is, for some applications of theinvention, stabilizing element 1062 is configured (e.g., dimensioned) tobe placeable in a circumferential groove defined by prosthetic valve 42.When prosthetic valve 42 is deployed, and expands in the opening definedby stabilizing element 1062, stabilizing element 1062 is disposed in thegroove, thereby further facilitating coupling of the stabilizing elementto the prosthetic valve, e.g., by inhibiting axial movement of theprosthetic valve through the opening defined by the stabilizing element.

It is to be noted that, although stabilizing element 1062 is describedwith reference to FIGS. 46A-B as being coupled to support-anchoringelements 900, the scope of the present invention includes stabilizingelements coupled to other support-anchoring elements described herein,such as support-anchoring elements 66.

Reference is made to FIGS. 47A-C, which are schematic illustrations ofsequential steps in the implantation of implant 30, comprisingprosthetic valve 42 and prosthetic valve support 1040, which comprisesprosthetic valve support 1080, in accordance with some applications ofthe invention.

Prosthetic valve support 1080 comprises two stabilizing legs 910, whichcomprise stabilizing legs 910 a. Support 1080 and/or legs 910 a areconfigured such that, during deployment of support 1080 (e.g., from anovertube), legs 910 a automatically move toward a pre-definedstabilizing configuration thereof. For example, legs 910 a may comprisea shape-memory material that is biased (e.g., shape-set) to move thelegs toward the stabilizing configuration thereof.

FIG. 47A shows support 1080 during deployment thereof. Annular portion41 is disposed against the proximal (e.g., atrial) side of native valve23, and stabilizing legs 910 a are moving toward the stabilizingconfiguration thereof. That is, FIG. 47A is a ‘snapshot’ of support 1080immediately following the release thereof from a delivery tube.

FIG. 47B shows support 1080 following deployment thereof at native valve23. Stabilizing legs 910 a have moved into the stabilizing configurationthereof. As described hereinabove, mutatis mutandis, for stabilizinglegs 910, with reference to FIG. 36A, proximal portion 912 of each legis disposed on a plane between (1) a plane 999 that is orthogonal to aplane defined by upstream support portion 41, and (2) a position inwhich the leg touches a part of upstream support portion 41 that isperipheral to inner edge 68.

FIG. 47C shows prosthetic valve 42 following deployment thereof in thelumen of support 1080. Typically, and as shown in FIG. 47C, the primarystructural element of prosthetic valve 42 defines plane 999, that isorthogonal to the plane defined by upstream support portion 41. That is,in the stabilizing configuration thereof, stabilizing legs 910 a aretypically disposed on a plane between (1) a plane defined by the primarystructural element of prosthetic valve 42, and (2) a plane defined byupstream support portion 41.

Reference is made to FIGS. 48A-C, which are schematic illustrations ofsequential steps in the implantation of implant 30, comprisingprosthetic valve 42 and prosthetic valve support 1040, which comprisesprosthetic valve support 1090, in accordance with some applications ofthe invention. Prosthetic valve support 1090 comprises two stabilizinglegs 910, which comprise stabilizing legs 910 b.

FIG. 48A shows prosthetic valve support 1090 in an at-rest configurationthereof, subsequent to deployment of the support at native valve 23.Support 1090 and/or legs 910 b are configured such that, subsequent todeployment of support 1090 (e.g., from an overtube), legs 910 b aredisposed proximal to upstream support portion 41 (e.g., atrially). Forexample, legs 910 b may comprise a shape-memory material that is biased(e.g., shape-set) to move the legs toward the at-rest configuration.

FIG. 48B shows prosthetic valve 42, in a compressed configurationthereof, disposed within a delivery tube 60, being delivered to nativevalve 23. Prosthetic valve 42 is moved distally into the lumen definedby upstream support portion 41. Stabilizing legs 910 b move (e.g.,rotate) through the lumen, responsively to the movement of theprosthetic valve. For example, distal movement of the prosthetic valvemay directly push the stabilizing legs through the lumen. Alternativelyor additionally, prosthetic valve 42 and/or stabilizing legs 910 b maycomprise engaging elements (e.g., barbs and/or levers) which facilitatethe movement of the stabilizing legs in response to the movement of theprosthetic valve.

FIG. 48C shows prosthetic valve 42 following deployment thereof in thelumen of support 1090. Stabilizing legs 910 b have moved into thestabilizing configuration thereof. Typically, and as shown in FIG. 48C,the primary structural element of prosthetic valve 42 defines plane 999,that is orthogonal to the plane defined by upstream support portion 41.That is, in the stabilizing configuration thereof, stabilizing legs 910b are typically disposed on a plane between (1) a plane defined by theprimary structural element of prosthetic valve 42, and (2) a planedefined by upstream support portion 41.

Reference is made to FIG. 49, which is a schematic illustration ofprosthetic valve support 40, embodied as a prosthetic valve support 4040a, in accordance with some applications of the invention. Prostheticvalve support 4040 a comprises a cylindrical element 90 that isconfigured to extend distally through native valve 23. Cylindricalelement 90 is typically configured to (1) facilitate coupling ofprosthetic valve support 4040 a to the native valve, and/or sealingtherebetween, (2) to facilitate coupling of prosthetic valve support4040 a to prosthetic valve 42 (or any other prosthetic valve describedherein), and/or sealing therebetween, and/or (3) to push aside nativeleaflets 82 of native valve 23. For such applications of the presentinvention in which prosthetic valve support 40 (i.e., prosthetic valvesupport 4040 a) comprises cylindrical element 90, support 40 andprosthetic valve 42 may be implanted in a manner as describedhereinabove with reference to FIGS. 1A-H.

Reference is made to FIG. 50, which is a schematic illustration of analternative technique for the implantation of implant 30, in accordancewith some applications of the invention. FIG. 50 shows a technique inwhich prosthetic valve 42 (shown crimped within delivery tube 60) isadvanced within ventricle 28 prior to and/or in conjunction with thedeployment of support 40.

Reference is now made to FIGS. 1A-H and 50. FIGS. 1A-H illustrate theimplantation of implant 30, whereby prosthetic valve support 40 isinitially delivered and placed against the annulus of the native valve,and subsequently, prosthetic valve 42 is delivered to the native valve.In some applications of the invention, as shown in FIG. 50, these twocomponents of implant 30 are delivered in reverse order. FIG. 50illustrates (1) the undeployed prosthetic valve 42, having beeninitially delivered to ventricle 28, and (2) prosthetic valve support 40being subsequently and/or in conjunction, delivered and deployed withinatrium 26. In these applications of the invention, following deploymentand positioning of prosthetic valve support 40 against the annulus ofnative valve 23, prosthetic valve 42 is moved atrially (i.e.,proximally) into the respective lumens of the native valve andprosthetic valve support 40, and is deployed, as described hereinabovewith reference to FIGS. 1G-H.

It is to be noted that implants 30 described herein may be implantedusing the method described hereinabove with reference to FIGS. 1A-H, orusing the method described hereinabove with reference to FIG. 50.

Reference is made to FIGS. 51A-B, which are schematic illustrations ofprosthetic valve support 40, comprising respective prosthetic valvesupports 4040 b and 4040 c which each comprise one or more wings 100, inaccordance with respective applications of the invention. Prostheticvalve support 40 is generally annular and is shaped to define a lumen.Wings 100 are configured and positioned with respect to prosthetic valvesupports 4040 b and 4040 c so as to provide one or more of the followingadvantages: (1) Increasing the stability of the support on the atrialsurface of the native valve annulus during the implantation procedureand/or post-implantation. (2) Distributing forces more evenly across theannulus of the native valve. (3) Restricting movement of native valveleaflets. (4) Preventing tilting of support 40 and subsequentinterference with the LVOT.

Wings 100 typically increase a ratio of surface area of the support toannular tissue. Wings 100 typically protrude between 5 mm and 40 mm(e.g., between 10 mm and 30 mm) from outer edge 69 of the support.Prosthetic valve support 4040 b comprises two wings, as shown in FIG.51A, typically positioned spaced apart from each other by 80-150degrees, as shown. Prosthetic valve support 4040 c comprises threewings, as shown in FIG. 51B, typically positioned spaced apart from eachother by 80-150 degrees (e.g., by 120 degrees, as shown). Otherquantities and configurations of wings 100 may be used in order tooptimize the positioning and/or stability of prosthetic valve support40.

In some applications of the invention, prosthetic valve support 40(e.g., prosthetic valve supports 4040 a, 4040 b, 4040 c) comprises barbs102, which protrude into the lumen defined by support 40. During theexpansion of prosthetic valve 42 within the lumen of support 40, asdescribed hereinabove, barbs 102 protrude into and engage prostheticvalve 42. Barbs 102 thereby facilitate coupling between support 40 andprosthetic valve 42 in addition to the radial forces between support 40and prosthetic valve 42. In some applications of the invention, some orall of barbs 102 may be curved, as shown in the enlarged images of FIGS.51A-B. Typically, the curved barbs curve away from the transverse planeof prosthetic valve support 40, such that, when implanted, barbs 102point proximally (i.e., into atrium 26). The applications of theinvention described with reference to FIGS. 51A-B may be used incombination with other applications of the invention described herein(i.e., applications described herein in which prosthetic valve support40 is used).

Reference is made to FIG. 52, which is a schematic illustration ofprosthetic valve 42 which comprises a variable-dimensioned valve 4042 a,in accordance with some applications of the present invention. Asdescribed hereinabove, expansion of prosthetic valve 42 in the lumen ofprosthetic valve support 40 creates radial force between prostheticvalve support 40 and prosthetic valve 42, which facilitates coupling ofprosthetic valve 42 to prosthetic valve support 40. In some applicationsof the present invention, a proximal portion 110 (e.g., the atrial end)of structural element 130 of prosthetic valve 4042 a expands such thatit assumes a dimension larger than the lumen defined by support 40(i.e., such that portion 110 has a longest length measured from a firstpoint of portion 110 to a second point of portion 110 opposite the firstpoint of portion 110 at a transverse cross-section of portion 110, whichis larger than a longest length of the lumen of support 40 measured froma first point on support 40 to a second point of support 40 opposite thefirst point of support 40 at the transverse cross-section). Typically,proximal portion 110 expands more than distal portions of prostheticvalve 4042 a. For example, portion 110 expands more than at least theportion of prosthetic valve 4042 a that is disposed within the lumen ofsupport 40. For some applications of the present invention, portion 110expands more than at least the distal end of valve 4042 a (e.g., theportion of valve 42 designated for positioning within ventricle 28).

As illustrated in FIG. 52, proximal portion 110 may be trumpet-shaped.Alternatively, proximal portion 110 may be frustoconical, or may be anyother configuration that has a dimension larger than the lumen definedby prosthetic valve support 40. The extra expansion of proximal portion110 described hereinabove provides axial resistance against undesireddistal (i.e., ventricular) movement of prosthetic valve 4042 a withrespect to support 40, in addition to the resistance provided by theradially expansive forces between prosthetic valve 42 (i.e., prostheticvalve 4042 a) and prosthetic valve support 40, as described hereinabove.The extra expansion of proximal portion 110 is further hypothesized tofacilitate release of proximal portion 110 from delivery apparatus (e.g., from a pushing member, from coupling tabs 4146, and/or from troughs222, described hereinbelow with reference to FIGS. 62A-D and 63A-B)thereby facilitating deployment of prosthetic valve 4042 a. Furthermore,the shape of prosthetic valve 4042 a is hypothesized to facilitate itsalignment with respect to prosthetic valve support 40 and/or nativevalve 23 (e.g., to be at least in part self-righting, at least duringdeployment).

In FIG. 52, prosthetic valve 4042 a is illustrated by a solid surfacefor clarity of illustration. It is to be noted that, typically,prosthetic valve 42 comprises a lattice structure as describedhereinabove. The application of the present invention described withreference to FIG. 52 may be used in combination with applications of thepresent invention described herein (i.e., applications for whichprosthetic valve 42 is used).

Reference is made to FIGS. 53A-C, which are schematic illustrations ofprosthetic valve 42 comprising an integrally-anchoring prosthetic valve42 b, which comprises valve-anchoring elements 64 comprising a pluralityof integral anchors 300, in accordance with some applications of thepresent invention.

Reference is now made to FIG. 53A, which is a schematic illustration ofprosthetic valve 42 b, in planar/flattened view in which prostheticvalve 42 b is cut longitudinally and flattened, for clarity ofillustration. It is to be noted, however, that the configuration shownin FIG. 53B defines the configuration of valve 42 b in an assembled,crimped state. Prosthetic valve 42 b comprises a lattice structure,comprising a plurality of struts which typically collectively define atessellation of shapes 128, e.g., generally-quadrilateral shapes, asshown. In the application of the present invention illustrated in FIGS.53A-C, the shapes 128 that form the lattice structure include crudediamonds 120 or crude kite-shapes (i.e., deltoids) 122, or a combinationthereof. It is to be noted that the scope of the present inventionincludes prosthetic valves having a tessellation of one or a combinationof other shapes.

The lattice structure of prosthetic valve 42 b further defines aplurality of voids 126. Shapes 128 are typically arranged in columns118, each shape connected to the next in each column. In some regions ofthe prosthetic valve, there is a separation 124 between a distal shapeand an adjacent shape (e.g., between the final shape in a column and arespective penultimate shape in the column that is longitudinallyproximal to the distal quadrilateral). This separation 124 allows aportion of the shape to move or be moved out of the plane of thelattice, thereby protruding from primary structural element 130 ofprosthetic valve 42 b when the distal portion of prosthetic valve 42 bis expanded. The protruding portion of shapes 128 thereby form integralanchors 300, which are typically configured to anchor prosthetic valve42 b to native valve 23. Valve-anchoring elements 64 are thereby formedfrom integral parts of the lattice structure that forms prosthetic valve42 b, and are disposed between a proximal end 251 and a distal end 252of primary structural element 130 of prosthetic valve 42 b. That is,prosthetic valve 42 b has a functional length (i.e., a length selectedso as to facilitate prosthetic valve function), and integral anchors 300typically do not increase the length of prosthetic valve 42 b to begreater than the functional length.

Reference is made to FIGS. 53B-C, which are schematic illustrations ofsequential steps of prosthetic valve 42 b being implanted.

Reference is now made to FIG. 53B. Prosthetic valve 42 b is compressible(e.g., crimpable) and expandable, and typically comprises a shape-memorymaterial (e.g., nitinol). Prosthetic valve 42 b is configured (e.g.,shape-set) such that valve-anchoring elements 64, embodied as integralanchors 300, are biased to protrude from the surface of primarystructural element 130. In this application of the present invention,primary structural element 130 of prosthetic valve 42 b is generallycylindrical, and integral anchors 300 protrude radially from the surfaceof the cylinder. Because integral anchors 300 are formed from theregular repeating structure of the lattice that forms prosthetic valve42 b, anchors 300 fit back into the plane of structural element 130 whenvalve 42 b is crimped into delivery tube 60, prior to and even duringimplantation. Integral anchors 300, thereby typically do not increasethe length nor the transverse cross-sectional longest dimension of thecrimped configuration of prosthetic valve 42, as compared to those ofany other prosthetic valves that do not comprise valve-anchoringelements 64 or that comprise elements 64 at a distal end thereof.

As described hereinabove, prosthetic valve 42 is deployed by distalmovement out of delivery tube 60. FIG. 53B shows prosthetic valve 42 bin a partially-deployed state, such that integral anchors 300 haveemerged from delivery tube 60, and have assumed an unconstrained,expanded, resting configuration in which the integral anchors 300protrude from the surface of primary structural element 130 of theprosthetic valve. In an expanded state of at least the distal portion ofvalve 42 b, as shown in FIG. 53B, integral anchors 300 typicallyprotrude up to and including 110 degrees (e.g., between 45 and 90, suchas between 45 and 60 degrees) from the surface of primary structuralelement 130, in a resting state of anchors 300. That is, in theprotruded state, the proximal portions of anchors 300 are distancedfurther from structural element than the distal portions of anchors 300which function as the pivot joints 4074 between anchors 300 andstructural element 130, as shown in the enlarged image of FIG. 53B.Typically, this partial deployment of prosthetic valve 42 is performedon the distal side of native heart valve 23 (e.g., the ventricular sideof mitral valve 24).

Reference is now made to FIG. 53C. Following the movement of integralanchors 300 into their unconstrained, protruding, configuration,prosthetic valve 42 b is pulled proximally (i.e., toward atrium 26),along with delivery tube 60. This proximal movement causes integralanchors 300 to abut against and capture leaflets 82 of the native valvein order to anchor prosthetic valve 42 b to the ventricular side of thenative valve. Typically, integral anchors 300 capture leaflets 82 of thenative valve by sandwiching leaflets 82 against primary structuralelement 130 of prosthetic valve 42 b and/or against the wall ofventricle 28. Typically, but not necessarily, integral anchors 300protrude between chordae tendineae 80 of the native valve.

Typically, the anchoring of the prosthetic valve and/or the capturing ofleaflets of the native valve are performed while prosthetic valve 42 bis partially deployed from delivery tube 60, as shown in FIG. 53C.Prosthetic valve 42 b is then fully deployed by moving delivery tube 60proximally with respect to valve 42 b, thereby sliding the delivery tubeoff of the prosthetic valve and allowing the prosthetic valve to expand.Such expanding of prosthetic valve 42 b facilitates coupling of theprosthetic valve to support 40, as described with reference to FIG. 1G.

Reference is made to FIGS. 54A-D, which are schematic illustrations ofprosthetic valve 42 comprising an integrally-anchoring prosthetic valve42 c, which comprises valve-anchoring elements 64 comprising a pluralityof integral anchors 310, in accordance with some applications of thepresent invention.

Integral anchors 310 are similar in form and function to integralanchors 300, and are typically formed by separations 124 in the latticestructure of structural element 130, as described with reference toFIGS. 53A-C. Integral anchors 310 are configured (e.g., shape-set) so asprotrude from primary structural element 130 of prosthetic valve 42 c,typically at a more acute angle than integral anchors 300 of FIGS. 53A-Cprotrude from prosthetic valve 42 b. For example, integral anchors 310may have an unconstrained, expanded, resting configuration in anexpanded state of at least the distal portion of prosthetic valve 42 c,in which anchors 310 protrude up to and including 110 degrees (e.g., upto and including 60 degrees, or between 5 and 80 degrees, or between 5and 40 degrees) from the surface of primary structural element 130 in aresting state of anchors 310. Integral anchors 310 can be deformed by adeforming force (e.g., by pushing tube 60 distally against pivot joints4074 between anchors 310 and structural element 130, as describedhereinbelow) into a further-expanded configuration, in which anchors 310protrude at a greater angle from the surface of primary structuralelement 130 than the angle of the resting configuration of anchors 310;thus, integral anchors 310 may be considered more open in thisconfiguration than they are in their resting configuration. In thisfurther-expanded, open configuration, integral anchors 310 typically aremade to protrude up to and including 160 degrees (e.g., between 30 and110 degrees, such as between 60 and 110 degrees) from the surface ofstructural element 130 of prosthetic valve 42 c. Since anchors 310 havea shape memory of assuming the resting state in the absence of forceapplied thereto, integral anchors 310 return toward the resting stateupon removal of the deforming force (e.g., once tube 60 is not pusheddistally against pivot joints 4074).

As described hereinabove, prosthetic valve 42 is deployed by distalmovement out of delivery tube 60. FIG. 54A shows prosthetic valve 42 cin a partially-deployed state, such that integral anchors 310 haveemerged from delivery tube 60, and have assumed the unconstrained,expanded resting configuration described hereinabove. Typically, thispartial deployment of prosthetic valve 42 is performed on the distalside of native heart valve 23 (e.g., the ventricular side of mitralvalve 24).

Reference is now made to FIG. 54B. Following partial deployment ofprosthetic valve 42 c, the prosthetic valve is moved proximally withrespect to delivery tube 60 (e.g., prosthetic valve 42 c is movedproximally while delivery tube 60 remains stationary, or prostheticvalve 42 c remains stationary while delivery tube 60 is moved distally,or prosthetic valve 42 c is moved proximally while delivery tube 60 ismoved distally). The distal end of delivery tube 60 is thereby pushedbetween primary structural element 130 and integral anchors 310, andprovides the deforming force that pushes the integral anchors towardtheir further-expanded open configuration, described hereinabove.

Reference is now made to FIG. 54C. Delivery tube 60 and prosthetic valve42 c are pulled proximally (i.e., toward atrium 26). This proximalmovement causes the open integral anchors 310 to engage leaflets 82 ofthe native valve, as described hereinabove.

Reference is now made to FIG. 54D. Delivery tube 60 is moved proximallywith respect to prosthetic valve 42 c (e.g., by withdrawing deliverytube 60 proximally), thereby removing the deforming force on anchors310. As described hereinabove, this removal of the deforming forcereleases integral anchors 310, which are thereby allowed to returntoward their resting state, to (1) clamp the chordae tendineae 80 and/orleaflets 82 of native valve 23 against primary structural element 130 ofprosthetic valve 42 c, and (2) anchor the prosthetic valve to theventricular side of the native valve. Typically, prosthetic valve 42 isthen fully deployed from delivery tube 60 (e.g., by retracting tube 60with respect to valve 42), thereby allowing radial expansion of theprosthetic valve to couple prosthetic valve 42 to prosthetic valvesupport 40, as described hereinabove.

Reference is now made to FIGS. 53A-C and 54A-C. For such applications ofthe present invention in which prosthetic valve 42 (i.e., prostheticvalves 42 b and/or 42 c) comprises integral anchors 300 and/or 310,prosthetic valve support 40 and prosthetic valve 42 may be implanted ina manner as described hereinabove with reference to FIGS. 1A-H. Thescope of the present invention includes implantation of implant 30 in amanner whereby prosthetic valve 42 is delivered to native valve 23and/or at least partially deployed, prior to the deployment of support40 (e.g., as described hereinabove with reference to FIG. 50).

Reference is made to FIGS. 55A-E, which are schematic illustrations ofprosthetic valve 42 comprising a twisted-anchor-based prosthetic valve42 d, which comprises valve-anchoring elements 64 comprising twistedanchors 320, in accordance with some application of the invention.

FIGS. 55A-B show valve-anchoring elements 64, comprising twisted anchors320, in their constrained and unconstrained configurations,respectively. Prosthetic valve 42 d typically comprises a shape-memorymaterial (e.g., nitinol), shaped to define a lattice structure. Thelattice structure comprises a plurality of struts which typicallycollectively define a tessellation of shapes 128 (e.g., crude diamonds120). Prosthetic valve 42 d comprises one or more twisted anchors 320,disposed at the distal end of prosthetic valve 42 d.

As described hereinabove, valve-anchoring elements 64 typically have aconstrained configuration for delivery, and an unconstrainedconfiguration whereby they protrude radially from primary structuralelement 130 of prosthetic valve 42. For some applications, in theconstrained configuration of elements 64, during delivery, elements 64are typically but not necessarily disposed distal to thegenerally-cylindrical structure of valve 42 at an angle that is between165 and 180 degrees with respect to the generally-cylindrical structure.In order to achieve these constrained and unconstrained configurationsfor prosthetic valve 42 d, comprising twisted anchors 320, a distalportion of prosthetic valve 42 d is typically torsionally bent to definetwisted anchors 320. For some applications of the present invention, inorder to achieve these configurations for prosthetic valve 42 dcomprising twisted anchors 320, a distal portion of prosthetic valve 42d is typically bent to define twisted anchors 320.

The material comprising the lattice structure of prosthetic valve 42 hasa depth 242 and each strut of the lattice structure has a width 244(shown in FIG. 55B). Typically, depth 242 is greater than width 244.Depth 242 is typically between 0.15 mm and 1.1 mm (e.g., between 0.3 mmand 0.6 mm) and width 244 is typically between 0.05 mm and 0.9 mm,(e.g., between 0.1 mm and 0.4 mm). In this application of the invention,the bending comprises twisting in the vicinity of a bending region 240,such that a bend axis 246 (shown in FIG. 55B) is substantially parallelto depth 242 in a vicinity of a distal portion of bending region 240.That is, a bend radius 248 lies on a plane that is substantiallyparallel to the relatively smaller width 244, thereby allowing a smallerthickness of material to be bent, compared to if bend radius 248 wereparallel with the relatively greater depth 242.

It is hypothesized that this configuration allows a greater bend angleto be imparted, such that twisted anchors 320 can (1) be disposed distalto (e.g., planar with) primary structural element 130 of prostheticvalve 42 d when the twisted anchors are in their constrainedconfiguration (i.e., when compressed in delivery tube 60 for delivery)as shown in FIG. 55A, and (2) pivot greater than 90 degrees (e.g.,greater than 110 degrees, greater than 120 degrees, or greater than 150degrees), to protrude radially from primary structural element 130 whenin their unconstrained configuration (i.e., following deployment of atleast the distal portion of prosthetic valve 42 d).

It is to be noted, that during delivery of prosthetic valve 42 d towardmitral valve 24, valve 42 d is crimped within delivery tube 60 such thatanchors 320 assume a constrained and compressed state within tube 60.

Reference is now made to FIGS. 55C-E, which are schematic illustrationsof sequential steps in the deployment and retrieval of prosthetic valve42 d that comprises twisted anchors 320. FIG. 55C shows delivery tube 60being moved proximally with respect to prosthetic valve 42 d (e.g.,prosthetic valve 42 d is moved distally while delivery tube 60 remainsstationary, or prosthetic valve 42 d remains stationary while deliverytube 60 is moved proximally, or prosthetic valve 42 d is moved distallywhile delivery tube 60 is moved proximally). Twisted anchors 320(disposed at a distal portion of valve 42), emerge first from withintube 60 and begin to move from their constrained and compressedconfiguration toward their unconstrained and expanded configuration onceexposed from within tube 60.

Reference is now made to FIG. 55D. Delivery tube 60 is moved furtherproximally, such that prosthetic valve 42 d is partially deployed towardits expanded configuration. Because delivery tube 60 clears anchors 320,twisted anchors 320 typically assume their resting unconstrainedconfiguration. The physician may proceed to couple prosthetic valve 42 dto the native valve and/or to prosthetic valve support 40, as describedwith reference to FIGS. 1F-G.

Reference is now made to FIG. 55E. Valve-anchoring elements 64comprising twisted anchors 320, facilitate retrieval of prosthetic valve42 d into delivery tube 60. Should it be necessary and/or desirable,while a proximal portion of valve 42 d is still crimped within tube 60,delivery tube 60 may be moved distally with respect to prosthetic valve42 d (e.g., prosthetic valve 42 d is moved proximally while deliverytube 60 remains stationary, prosthetic valve 42 d remains stationarywhile delivery tube 60 is moved distally, or prosthetic valve 42 d ismoved proximally while delivery tube 60 is moved distally), therebyrecompressing prosthetic valve 42 d into the delivery tube. Twistedanchors 320 are pushed distally by delivery tube 60, such that they mayalso by straightened, as shown, and subsequently enter the deliverytube. Prosthetic valve 42 d may then be repositioned and redeployed, ormay be removed from the subject.

In some applications of the invention, twisted anchors 320 comprise morethan one bending region 240. For such applications, the materialcomprising prosthetic valve 42 d is bent and twisted in each respectivebending region, as described with reference to FIGS. 55A-B. For example,one bending region may be longitudinally proximal (i.e., coaxial) withrespect to another bending region. Twisted anchors 320 that comprisemore than one bending region are hypothesized to have enhanced pivotingability compared to valve-anchoring elements that comprise one bendingregion. That is, twisted anchors 320 having more than one bending regionenable anchors 320 to move more than 90 degrees, e.g., more than 160degrees, with respect to a surface of structural element 130. Forexample, twisted anchors 320 may pivot such that they clamp leaflets 82of the native valve against primary structural element 130 of prostheticvalve 42, thereby anchoring the prosthetic valve to the native valve.

Reference is made to FIGS. 56A-D, which are schematic illustrations ofprosthetic valve 42 comprising a clip-on prosthetic valve 42 e, whichcomprises valve-anchoring elements 64 that comprise loop-shapedvalve-anchoring elements 200 arranged in pairs 132 to form clips 65 a,in accordance with some applications of the invention.

Reference is now made to FIG. 56A. As described hereinabove, prostheticvalve 42 is compressible (e.g., crimpable) and expandable, and typicallycomprises a shape-memory material (e.g., nitinol). In this applicationof the invention, prosthetic valve 42 e comprises loop-shapedvalve-anchoring elements 200, arranged in pairs 132. Typically, a firstloop-shaped valve-anchoring element 200 a in each pair is smaller than asecond loop-shaped valve-anchoring element 200 b, such that firstloop-shaped element 200 a is disposable within and/or passable through aspace defined by the larger loop shape of second loop-shapedvalve-anchoring element 200 b. It is to be noted that the scope of thepresent invention includes other configurations and arrangements ofelements 200.

It is to be noted that the scope of the present invention includes afirst loop-shaped valve-anchoring element 200 a being larger than secondloop-shaped valve-anchoring element 200 b, such that second loop-shapedelement 200 b is disposable within and/or passable through a spacedefined by the larger loop shape of first loop-shaped valve-anchoringelement 200 a.

As described hereinabove, valve-anchoring elements 64 have a constrainedand compressed configuration for delivery of prosthetic valve 42 e (asshown in FIG. 56A), and an unconstrained, expanded configuration whenprosthetic valve 42 e is deployed (as shown in FIG. 56B).

Loop-shaped valve-anchoring elements 200 are shown in FIG. 56A in theirconstrained configuration in which second loop-shaped valve-anchoringelement 200 b of each pair 132 is typically disposed distal to primarystructural element 130, and first loop-shaped valve-anchoring element200 a of each pair 132 is typically disposed against the surface ofprimary structural element 130. That is, in their constrainedconfiguration, loop-shaped valve-anchoring elements 200 are typicallylongitudinally aligned.

FIG. 56B shows loop-shaped valve-anchoring elements 200 in theirunconstrained, expanded configuration. Movement from the constrainedconfiguration to the unconstrained configuration of elements 200typically comprises (1) pivoting proximally of second valve-anchoringelement 200 b of each pair 132, and (2) pivoting distally of firstvalve-anchoring element 200 a of each pair 132. In some applications ofthe invention, in the unconstrained configuration, the planes defined bythe two valve-anchoring elements 200 of each pair 132 are generallyaligned (e.g., within 20 degrees of each other).

In some applications of the invention, in the unconstrainedconfiguration, a rounded end of second valve-anchoring element 200 b ofeach pair 132 is disposed more proximally than a rounded end of firstvalve-anchoring element 200 a. In such applications, movement ofvalve-anchoring elements 200 from the constrained configuration to theunconstrained configuration comprises movement of the rounded ends ofthe second valve-anchoring elements 200 b of each pair 132 proximallypast the respective rounded ends of the first valve anchoring elements200 a of each pair 132.

In either application, movement of valve-anchoring elements 200 from theconstrained configuration to the unconstrained configuration allowselements 200 a and 200 b to capture material (e.g., leaflets 82 of thenative valve) between them, i.e., in a manner in which elements 200 aand 200 b function together as a clip 65 a.

FIGS. 56C-D show sequential steps in the implantation of prostheticvalve 42 e. FIG. 56C shows prosthetic valve 42 e disposed in a crimpedconfiguration in delivery tube 60. Delivery tube 60 is moved proximallywith respect to prosthetic valve 42 e, such that only loop-shapedvalve-anchoring elements 200 b (i.e., the first-deployed anchoringelements) of each pair 132 are released and move toward theirunconstrained configuration, typically by pivoting in a proximaldirection and in a direction toward the ventricular surface ofrespective leaflets 82.

Typically, following the deployment of elements 200 b at the respectiveventricular surfaces of leaflets 82, elements 200 a are positionedwithin tube 60 in a manner in which during their expansion from withintube 60, elements 200 a move toward respective atrial surfaces ofleaflets 82. For some applications, following the deploying of elements200 b, valve 42 e is pulled proximally (e.g., by pulling proximally onboth valve 42 e and tube 60) in order to adjust the positioning of valve42 e with respect to leaflets 82 and so as to ensure that, once deployedfrom within tube 60, elements 200 a will press against respective atrialsurfaces of leaflets 82.

FIG. 56D shows delivery tube 60 having been removed (i.e., by beingretracted) from the body of the subject. During the retracting of tube60 loop-shaped valve-anchoring elements 200 a (i.e., the second-deployedanchoring elements) of each pair are deployed such that elements 200 amove toward their unconstrained configuration, typically by pivoting ina distal direction and in a direction toward the atrial surfaces ofrespective leaflets 82. Leaflets 82 of the native valve are therebyclamped between the two loop-shaped valve-anchoring elements 200 a and200 b of each pair 132, thereby anchoring prosthetic valve 42 e tonative valve 23. Thus, pairs 132 of loop-shaped valve-anchoring elements200 function as clips 65 a.

Reference is made to FIGS. 57A-D, which are schematic illustrations ofprosthetic valve 42 comprising a clip-on prosthetic valve 42 f, whichcomprises valve-anchoring elements 64 that comprise clips 65 b, inaccordance with some applications of the invention.

FIG. 57A shows clips 65 b being typically coupled to the distal end ofprimary structural element 130 of prosthetic valve 42 f. Typically,clips 65 b are flexibly coupled to prosthetic valve 42 f, i.e.,valve-coupling elements 64 are configured such that clips 65 b are ableto move with respect to prosthetic valve 42 f. During the implantationof prosthetic valve 42 f, clips 65 b are clipped to leaflets 82 and/orchordae tendineae 80 of the native valve, thereby anchoring theprosthetic valve to the native valve. FIG. 57A shows two valve-anchoringelements 64 comprising respective clips 65 b, disposed on opposite sidesof the distal end of prosthetic valve 42 f. It is to be noted that thescope of the present invention includes prosthetic valves 42 f havingany suitable quantity and arrangement of clips 65 b, depending on thetechnique used and the individual anatomy of the subject.

Typically, during advancement of valve 42 f, valve 42 f is crimpedwithin delivery tube 60.

FIG. 57B shows prosthetic valve 42 f being partially deployed fromdelivery tube 60, such that clips 65 b are disposed outside of thedelivery tube. Clips 65 b are coupled to leaflets 82 of the nativevalve, holding the leaflets and drawing them close to the primarystructural element 130 of prosthetic valve 42 f. For some applications,clips 65 b have a tendency to close, and are held open during deliveryof valve 42 f by a force applied to clips 65 b (e.g., by a pull wire).In the absence of the force applied to clips 65 b, clips 65 b closearound respective leaflets 82. For other applications, the opening andclosing of clips 65 b are remotely controlled by the operatingphysician. Typically, clips 65 b may be opened and closed repeatedlyuntil a firm grasping of leaflets 82 is achieved. Clips 65 b aretypically configured such that they do not cause substantial damage toleaflets 82.

FIG. 57C is a top-view schematic illustration of prosthetic valve 42 fin the partially-deployed state, as described hereinabove with referenceto FIG. 57B. While prosthetic valve 42 f is in a compressedconfiguration within delivery tube 60, it has a cross-sectional diametersmaller than that of the lumen defined by prosthetic valve support 40.Typically, clips 65 b couple parts of leaflets 82 (e.g., central parts,or part of leaflets 82 adjacent one another) to prosthetic valve 42 f,the remaining potions of leaflets 82 remain relatively free. Thisarrangement typically results in a double-orifice configuration ofnative valve 23, whereby native valve 23 (comprising a pair of leaflets82) can be considered to be divided into two orifices 86, on oppositesides of prosthetic valve 42 f, each orifice 86 being surrounded byrespective pairs of remaining portions of leaflets 82. It ishypothesized that, in this arrangement, the native valve can continue tofunction until prosthetic valve 42 f is fully deployed. It is furtherhypothesized that this double-orifice state provides even greateradvantage in applications of the invention where the prosthetic valve isdelivered before prosthetic valve support 40 (such as the application ofthe invention described with reference to FIG. 50). In such applicationsin which the prosthetic valve is delivered before support 40, theinterval between delivery and full deployment of the prosthetic valve istypically longer than in applications where prosthetic valve support 40is delivered and deployed before delivery of the prosthetic valve. Thus,for these applications, the double orifice created by the prostheticvalve facilitates blood flow from the atrium to the ventricle during theimplantation procedure.

FIG. 57D is a side-view schematic illustration of prosthetic valve 42 f,fully deployed in the annulus of the native valve. Valve-anchoringelements 64, comprising clips 65 b, couple leaflets 82 of the nativevalve to the primary structural element 130 of prosthetic valve 42,thereby anchoring the prosthetic valve to the native valve.

It is to be noted that the technique described with reference to FIGS.57A-D, in particular the ‘double-orifice’ configuration described withreference to FIG. 57C, may be used in combination with other prostheticvalves comprising tissue-engagement elements 62. In particular, thetechnique may be used where valve-anchoring elements 64 comprise clips65 or clip functionality, such as integral anchors 310, described withreference to FIGS. 54A-D, and/or twisted anchors 320, described withreference to FIGS. 55A-E, and/or pairs 132 loop-shaped valve-anchoringelements 200, described with reference to FIGS. 56A-D.

Reference is now made to FIGS. 52, 53A-C, 54A-C, 55A-E, 56A-D, and57A-D. It is to be noted that the scope of the present inventionincludes implanting the respective prosthetic valves 42 disclosed hereinat native valve 23 prior to implanting support 40. In such applicationsof the present invention, anchoring elements 64 enable prosthetic valves42 described herein to remain coupled to native valve 23 until support40 is positioned at the annulus of native valve 23. In suchapplications, leaflets 82 are brought closer together, temporarily in amanner which forms a double orifice in native valve 23 for blood to passfrom the atrium to the ventricle during the implantation procedure (asdescribed hereinabove with reference to FIG. 57C). Following thecoupling of prosthetic valve 42 to leaflets 82, support 40 is thenpositioned around the proximal portion of prosthetic valve 42 in orderto facilitate coupling of support 40 to valve 42 and provide the radialforce against valve 42 in order to maintain implanting of prostheticvalve 42 at native valve 23, as described hereinabove. In suchapplications, support 40 is positioned around the proximal portion ofprosthetic valve 42 when the proximal portion of prosthetic valve 42 iscrimped and compressed within tube 60 (for ease of positioning support40 around the proximal portion of valve 42).

Reference is made to FIGS. 58A-61C, which are schematic illustrations ofprosthetic valve support 40, embodied as anchoring prosthetic valvesupports 4040 d, 4040 e, and 4040 f, comprising tissue-engaging elements62, in accordance with respective applications of the invention. Inthese applications of the invention, tissue-engaging elements 62comprise support-anchoring elements 66, which anchor prosthetic valvesupport 40 to native valve 23. As described hereinabove, prostheticvalve support 40 is typically used in combination with prosthetic valve42. The anchoring of prosthetic valve support 40 to the native valveprovides one or more of the following advantages: (1) The deliveryapparatus used to deploy the prosthetic valve support (e.g., holdingmembers 46, described with reference to FIGS. 1C-F) may be removedfollowing implantation of support 40 and prior to delivering and/ordeploying prosthetic valve 42, thereby providing more space in atrium 26for the delivery and/or deployment of the prosthetic valve; (2) Implant30, comprising prosthetic valve 42 and prosthetic valve support 40, isanchored more securely to the native valve; and (3) Support-anchoringelements 66 contribute toward the capture of leaflets 82 of the nativevalve.

For some applications of the invention, it is hypothesized that theanchoring of support 40 to the native valve by support-anchoringelements 66 may be sufficient to anchor implant 30 to the native valve,thereby minimizing or even eliminating the need for supplementalanchoring of implant 30 by valve-securing elements 64. Therefore, forsuch applications of the invention, prosthetic valve 42 does notcomprise valve-anchoring elements 64. In some such applications of theinvention, leaflets 82 of the native valve are allowed to function, atleast in part, following implantation of the prosthetic valve.

Reference is now made to FIGS. 58A-D, which are schematic illustrationsof prosthetic valve support 40 comprising anchoring prosthetic valvesupport 4040 d, which comprises support-anchoring elements 66 comprisingfixed anchors 330, in accordance with some applications of theinvention.

During delivery of support 4040 d to the native valve, support 4040 d iscrimped within overtube 44, as described hereinabove with reference tosupport 40 of FIGS. 1B-C. FIG. 58A shows prosthetic valve support 4040 din its expanded configuration, as described hereinabove with referenceto support 40 in FIG. 1B. Typically, prosthetic valve support 4040 d isannular and is shaped to define an outer edge 69 and an inner edge 68.Outer edge 69 typically defines the diameter of the annular prostheticvalve support, and inner edge 68 typically defines the diameter of thelumen in which prosthetic valve 42 is typically disposed, as describedhereinabove. Support-anchoring elements 66 comprising fixed anchors 330,are typically coupled to inner edge 68.

In some applications of the invention, fixed anchors 330 comprisecoupling-portion 70 configured to engage tissue of the native valve.Coupling-portion 70 is illustrated as an extension of fixed anchors 330such that fixed anchors 330 assume a generally L-shape. In otherapplications of the invention, coupling-portion 70 may be disposeddifferently (e.g., at an angle other than the angle as shown), or maycomprise clips 65 a or 65 b, or another means for engaging native valve23. In some applications of the invention, fixed anchors 330 do notcomprise a coupling-portion.

FIG. 58B shows prosthetic valve support 4040 d, partially deployedproximal to native valve 23 (i.e., in atrium 26), as describedhereinabove (e.g., with reference to FIG. 1B). Fixed anchors 330 extenddistally from the semi-deployed prosthetic valve support, and are moveddistally, between the leaflets of the native valve.

Reference is now made to FIG. 58C. Fixed anchors 330 move apart asprosthetic valve support 4040 d expands to its fully-deployed, expandedconfiguration at native valve 23. That is, as inner edge 68 expands toassume its expanded state, the lumen of support 4040 d expands therebymoving apart anchors 330. Fixed anchors 330 engage leaflets 82 of thenative valve, thereby anchoring prosthetic valve support 4040 d to thenative valve. In some applications of the invention, fixed anchors 330are configured such that native leaflets 82 continue to function, atleast in part when support 4040 d is implanted. For example, in someapplications, the dimensions and relative positions of fixed anchors 330do not substantially restrict the movement of leaflets 82. For example,the total width of each of the fixed anchors 330 elements may be lessthan 1 mm. Furthermore, in some applications of the invention, theforces exerted on leaflets 82 by the flow of blood are hypothesized toovercome at least some of the force applied to leaflets 82 by therigidity of fixed anchors 330, i.e., in order to cause fixed anchors 330to flex as leaflets 82 move.

FIG. 58D is a schematic illustration of a transverse atrialcross-section of the fully-deployed prosthetic valve support describedwith reference to FIG. 58C. Fixed anchors 330 engage leaflets 82 of thenative valve, thereby anchoring prosthetic valve support 4040 d to thenative valve. Coupling-portions 70 are disposed on the distal (i.e.,ventricular) side of the native valve, and are therefore illustrated inphantom.

Reference is now made to FIGS. 59A-B, which are schematic illustrationsof anchoring prosthetic valve support 4040 d comprisingsupport-anchoring elements 66 comprising fixed anchors 330, inaccordance with some applications of the invention.

Anchoring prosthetic valve support 4040 d is anchored to native valve 23in a different orientation to that described with reference to FIGS.58A-D. FIG. 59A shows prosthetic valve support 40 fully deployed andanchored to native valve 23. Fixed anchors 330 extend toward, andengage, commissures 84 of the native valve, thereby anchoring prostheticvalve support 4040 d to the native valve.

FIG. 59B is a schematic illustration of a transverse atrialcross-section of the fully-deployed prosthetic valve support 4040 ddescribed with reference to FIG. 59A. Fixed anchors 330 engagecommissures 84 of the native valve, holding the leaflets apart atcommissures 84 and anchoring prosthetic valve support 4040 d to thenative valve. Coupling-portions 70 are disposed on the distal (i.e.,ventricular) side of the native valve, and are therefore illustrated inphantom. It is hypothesized that the orientation of prosthetic valvesupport 4040 d and positioning of fixed anchors 330, described withreference to FIGS. 59A-B, interferes less with leaflets 82, as comparedto the orientation and positioning of fixed anchors 330 described withreference to FIGS. 58C-D (i.e., fixed anchors 330 engaging respectiveportions of leaflets 82). This positioning of anchors 330 at commissures84, thereby allows the native valve to continue to function, at least inpart, until prosthetic valve 42 is deployed.

Reference is made to FIGS. 60A-B and 61A-C, which are schematicillustrations of prosthetic valve support 40 comprising prosthetic valvesupport 4040 e and 4040 f, respectively, in accordance with someapplications of the invention. Support-anchoring elements 66 in suchapplications comprise hinged anchors 340 that are typically coupled toinner edge 68 of support 40. In some applications of the invention,hinged anchors 340 comprise a coupling-portion 70, configured to engagetissue of the native valve. Coupling-portion 70 is illustrated as anextension of hinged anchors 340, thereby forming the hinged anchors intogenerally L-shapes. In other applications of the invention,coupling-portion 70 may be disposed differently (e.g., at an angledifferent to that as shown in FIGS. 60A-B and 61A-C), or may compriseclips 65 a or 65 b, or another means for engaging native valve 23. Insome applications of the invention, hinged anchors 340 do not comprise acoupling-portion.

Hinged anchors 340 are typically coupled to prosthetic valve support 40via a hinge point 72. Hinge point 72 may comprise a flexible materialand/or moving components. For some applications of the invention, hingedanchors 340 rotate freely around hinge point 72 as far as their shapeand juxtaposition allows. For some applications of the invention, hingedanchors 340 are biased to reside in a particular configuration. Forexample, hinged anchors 340 and/or hinge point 72 and/or prostheticvalve support 40 may comprise a shape-memory material (e.g., nitinol) ora spring mechanism, configured to push hinged anchors 340 radiallyoutward.

The use of hinge points 72 for coupling support-anchoring elements 66 toprosthetic valve support 40 is hypothesized to provide one or more ofthe following advantages: (1) Improving compressibility of prostheticvalve support 40, for transcatheter delivery. (2) Improving movement ofnative leaflets 82 following deployment of prosthetic valve support 40to the native valve. (3) Increasing adjustability of the dimensions andconfiguration of support-anchoring elements 66.

Reference is now made to FIGS. 60A-B, which are schematic illustrationsof prosthetic valve support 40 comprising hinged prosthetic valvesupport 4040 e, comprising hinged anchors 340, in accordance with someapplications of the invention. FIG. 60A shows prosthetic valve support4040 e in a fully-expanded configuration. Prosthetic valve 4040 e isconfigured such that hinged anchors 340 are biased to extend radiallyoutward.

FIG. 60B shows prosthetic valve support 4040 e fully deployed at nativevalve 23. As described with reference to FIGS. 58C-D and 59A-B,support-anchoring elements 66 may be positioned to engage commissures 84(FIGS. 59A-B) and/or leaflets 82 of the native valve (FIGS. 58C-D). Inthe application of the invention illustrated in FIG. 60B, prostheticvalve support 4040 e and hinged anchors 340 are configured such that thehinged anchors extend radially to engage the commissures 84 of thenative valve. For other applications, hinged anchors 340 are freelyrotatable, and are coupled to leaflets 82 such that support 40 isanchored to the native valve whilst allowing leaflets 82 to move.

Reference is made to FIGS. 61A-C, which are schematic illustrations ofprosthetic valve support 40 comprising free-hinged prosthetic valvesupport 40 f, comprising hinged anchors 340 comprisingclamping-hinged-anchors 350, in accordance with some applications of theinvention.

FIG. 61A shows prosthetic valve support 4040 f, comprising hingedanchors 350, in a fully-expanded configuration and a resting statethereof. Clamping-hinged-anchors 350 are coupled to prosthetic valvesupport 4040 f via hinge point 72 and are typically free to pivot aroundthe hinge point as far as their shape and juxtaposition allows.Coupling-portion 70 is shown in an unconstrained clamped configuration,in which it is typically configured to extend from structural component71 of clamping-hinged-anchor 350, at an acute angle (e.g., less than 80degrees, less than 45 degrees, or less than 20 degrees). In someapplications of the invention, coupling-portion 70 may be configured toextend at less than 1 degree, i.e., to touch the structural component 71of clamping-hinged-anchor 350. Clamping-hinged-anchors 350 typicallycomprise a shape-memory material (e.g., nitinol), such that they arecompressible into a compressed (e.g., crimped) configuration fordelivery, and are deformable and expandable at the site of implantation.

FIG. 61B shows clamping-hinged anchors 350 of prosthetic valve support4040 f, in a compressed configuration, e.g., for delivery toward thenative valve within overtube 44 (e.g., as described hereinabove withreference to support 40 in FIG. 1B). It is to be noted that overtube 44is not shown for clarity of illustration. Clamping-hinged-anchors 350are disposed distally to other parts of prosthetic valve support 4040 f.Prior to delivery, coupling-portions 70 are typically in an unclampedconfiguration, in which they extend further distally from prostheticvalve support 4040 f and from structural component 71 ofclamping-hinged-anchor 350. During deployment of prosthetic valvesupport 4040 f from overtube 44, clamping-hinged-anchors 350 areextended from within overtube 44 (coupling-portion 70 first followed bystructural component 71) and between leaflets 82 of native valve 23. Asclamping-hinged-anchors 350 are fully exposed from within overtube 44,they move toward their clamped configuration, and are allowed to assumetheir resting state (as shown in FIG. 61A) in which coupling-portion 70moves toward structural component 71 in order to clamp a portion ofleaflet 82 therebetween and to thereby anchor prosthetic valve support4040 f to the native valve.

FIG. 61C shows prosthetic valve support 4040 f fully deployed at nativevalve 23. Coupling-portions 70 clamp leaflets 82 against respectivestructural components 71 of clamping-hinged-anchors 350, as describedhereinabove. Thus, clamping-hinged-anchors 350 function as clips 65 c.As described hereinabove, clamping-hinged-anchors 350 are typically ableto rotate freely about hinge point 72 as far as their shape andjuxtaposition allows. Leaflets 82 are thereby able to move proximallyand distally (i.e., atrially and ventricularly), as illustrated by theupper and lower panels of FIG. 61C. Clamping-hinged-anchors 350 therebyallow native valve 23 to continue to function until prosthetic valve 42is deployed, as described hereinabove.

For some applications of the invention, prosthetic valve support 4040 fis configured such that clamping hinged anchors 350 are biased to extendradially inward (i.e., toward each other). This configuration isillustrated by the upper panel of FIG. 61C. In such applications of theinvention, leaflets 82 of the native valve are held together, forming adouble-orifice configuration, as described herein (e.g., with referenceto FIG. 57C). Clamping hinged anchors 350 thereby allow native valve 23to continue to function, at least in part, until prosthetic valve 42 isdeployed.

Reference is again made to FIGS. 58A-D, 59A-B, 60A-B and 61A-C. It is tobe noted that supports 40 described herein comprise twosupport-anchoring elements 66 by way of illustration and not limitation.That is, the scope of the present invention includes the supports 40comprising any suitable number and configuration of anchoring elements66. For example, valve support 40 may comprise four support-anchoringelements 66 configured such that a pair of elements 66 are anchored tocommissures 84 and a pair of elements 66 are anchored to leaflets 82 ofthe native valve.

Reference is now made to FIGS. 1, 49-61. It is to be noted thatapplications of tissue-engaging elements 62 described herein areinterchangeable as valve-anchoring elements 64, and/or assupport-anchoring elements 66. For example, pairs 132 of loop-shapedanchoring elements 200, described with reference to FIGS. 56A-D asvalve-anchoring elements 64, may be coupled to prosthetic valve support40 to the native valve (i.e., so as to function as support-anchoringelements 66). Similarly, clamping-hinged-anchors-350, for example,described with reference to FIGS. 61A-C as support-anchoring elements66, may be employed to couple prosthetic valve 42 to the native valve(i.e., and function as valve-anchoring elements 64).

Reference is made to FIGS. 62A-D, which are schematic illustrations ofdelivery apparatus 4138 a, used to deploy a medical device 150, inaccordance with some applications of the invention. As shown in FIG.62A, delivery apparatus 4138 a comprises a delivery tube 154 and apushing member 140 a. Pushing member 140 a comprises a support 4142 aand one or more coupling tabs 4146, extending from the support. In theapplication of the invention shown in FIG. 62A, support 4142 a comprisesa core 144, and coupling tabs 4146 extend radially from the core. Insome applications of the invention, support 4142 a is shaped to define aplate 4148 at the proximal end of support 4142 a. The dimensions andrelative positions of support 4142 a, tabs 4146, and plate 4148 may beadjusted for the specific medical device 150 to be deployed usingdelivery apparatus 4138 a.

In the application of the invention described with respect to FIGS.62A-D, medical device 150 comprises prosthetic valve 42 (e.g., any oneof prosthetic valves 42 described herein).

FIG. 62B shows prosthetic valve 42 in a compressed (i.e., crimped)configuration for delivery and deployment using delivery apparatus 4138a. As described hereinabove, prosthetic valve 42 typically has a latticestructure that defines a plurality of shapes, and voids 4126, and haselastic memory. Prosthetic valve 42 is shown in a compressed (e.g.,crimped) configuration, and as shown in the enlarged image, a proximalportion of valve 42 is disposed around core 144 of pushing member 140 asuch that each of coupling tabs 4146 is disposed within a respectivevoid 4126 defined by the lattice structure of the prosthetic valve.

Prosthetic valve 42 and pushing member 140 a are disposed within thelumen of delivery tube 154. Delivery tube 154 restricts expansion ofprosthetic valve 42, thereby holding the proximal portion of prostheticvalve 42 around core 144 of pushing member 140 a, in the configurationdescribed herein. Coupling tabs 4146 restrict movement of prostheticvalve 42 with respect to pushing member 140 a. Delivery tube 154therefore facilitates coupling of prosthetic valve 42 to pushing member140 a via coupling tabs 4146. In applications of the invention wherepushing member 140 a is shaped to define plate 4148, the plate typicallyfurther facilitates this coupling by restricting proximal movement ofprosthetic valve 42 with respect to the pushing member (e.g., byfunctioning as a cap).

FIG. 62C shows prosthetic valve 42 partially deployed from delivery tube154. Pushing member 140 a, and, thereby, prosthetic valve 42, are moveddistally through delivery tube 154.

A control tube 4152 is coupled at a distal end thereof to pushing member140 a (e.g., control tube 4152 is coupled to support 4142 a). Controltube 4152 is shaped so as to define a lumen through which a guidewiretube 4153 passes, and control tube 4152 is slidable with respect to andalong guidewire tube 4153. Guidewire tube 4153 houses guidewire 45described hereinabove. Control tube 4152 is slidably disposed within alumen of an overtube 4155.

Reference is again made to FIG. 62C. Pushing member 140 a is pusheddistally by pushing control tube 4152 along guidewire tube 4153 suchthat pushing member 140 a pushes prosthetic valve 42. As pushing member140 a pushes valve 42 distally, distal portions of the prosthetic valveexpand toward the expanded configuration as they become exposed fromdelivery tube 154, while the proximal end of valve 42 remains coupled topushing member 140 a via tabs 4146.

FIG. 62D shows prosthetic valve 42 having been fully deployed fromwithin delivery tube 154. Pushing member 140 a and prosthetic valve 42are moved further distally through delivery tube 154 by control tube4152. When the proximal portion of prosthetic valve 42 emerges fromwithin delivery tube 154, expansion of the proximal portion ofprosthetic valve 42 uncouples the prosthetic valve from coupling tabs4146 by expanding voids 4126 away from tabs 4146, thereby releasing theprosthetic valve from pushing member 140 a.

Should it be necessary and/or desirable during the procedure, untilmedical device 150 (e.g., prosthetic valve 42) is released from pushingmember 140 a (i.e., while the proximal portion of medical device 150 iscrimped within delivery tube 154), the remaining portions of medicaldevice 150 may be drawn back into delivery tube 154 (e.g., forrepositioning or withdrawal of the medical device).

Reference is now made to FIGS. 54A-D and 62A-D. It is to be noted thatfor some applications, withdrawing of a portion of prosthetic valve 42within delivery tube 154 facilitates deforming of integral anchors 310toward their constrained, further-expanded open configuration. Thisoccurs when a distal end of tube 154 pushes against pivot joint 4074between anchor 310 and structural element 130 as the portion ofprosthetic valve 42 is withdrawn.

In the application of the invention described with reference to FIGS.62A-D, voids 4126 are defined by the lattice structure of medical device150 (i.e., prosthetic valve 42). In other applications of the invention,voids in medical device 150 may be defined by other structural featuresof the medical device and not necessarily by a lattice structure.Typically, as described herein, coupling tabs 4146 couple medical device150 to pushing member 140 a at a proximal portion of the medical device,thereby retaining coupling of the medical device to pushing member 140 auntil the medical device is fully deployed from delivery tube 154. It isto be noted that the scope of the present invention includes tabs whichalternatively or additionally couple medical device 150 to pushingmember 140 a at portions of the medical device other than the proximalportion thereof.

It is hypothesized that utilization of pushing member 140 a, comprisingcoupling tabs 4146 that are disposable in voids 4126 defined by anexpandable medical device 150, (1) reduces the overall length of theapparatus (i.e., the combined lengths of medical device 150 and deliverytube 154) being advanced into the subject, and/or (2) reduces therequirement for additional components of medical device 150 whichfunction as coupling structures of medical device 150. That is, medicaldevice 150 has an integral coupling system by which voids 4126 arecoupled to tabs 4146. The applications of the invention described withreference to FIGS. 62A-D may be used in combination with applications ofthe invention described hereinabove, as well as for the delivery ofother expandable medical devices.

Reference is again made to FIGS. 1A-H, 9A-E, and 62A-D. It is to benoted that delivery tube 154 of FIGS. 9A-E and 62A-D may be similar to,may act as, and/or may comprise, overtube 44 and/or delivery tube 60 ofFIGS. 1A-H.

Reference is made to FIGS. 63A-B, which are schematic illustrations ofdelivery apparatus 4138 b, used to deploy an expandable medical device150, in accordance with some applications of the invention. Reference isnow made to FIG. 63A. Delivery apparatus 4138 b comprises delivery tube154 and a pushing member 140 b, which comprises a support 4142 b. Inthis application of the invention, pushing member 140 b is shaped todefine a plurality of troughs 222. Typically, troughs 222 run along thesurface of pushing member 140 b, from one end of the pushing member(e.g., a distal end) to a point along the length of the pushing member.Typically, troughs 222 are shaped so as to define a respective widenedpart 224 (e.g., at a proximal end of the trough) or is configured toopen into a larger widened part 224 (as shown). In the application ofthe invention described with reference to FIGS. 63A-B, widened part 224comprises a single circumferential groove surrounding the circumferenceof pushing member 140 b, into which all troughs 222 open. Alternatively,each trough 222 may be shaped so as to define a respective widened part.

Reference is now made to FIG. 63B. Medical device 150, embodied in thisapplication of the invention as expandable prosthetic valve 42,comprises a plurality of coupling tabs 220. Coupling tabs 220 areconfigured to be disposable in respective troughs 222 of pushing member140 b, such that troughs 222 restrict distal movement of medical device150. In the application of the invention described with reference toFIGS. 63A-B, coupling tabs 220 are T-shaped, so as to be disposable inrespective troughs 222 and in the circumferential groove that formswidened part 224. The disposition of coupling tabs 220 in troughs 222couples prosthetic valve 42 to pushing member 140 b. Coupling tabs 220,troughs 222, and widened part 224 may assume any shape that allows suchcoupling.

Prior to delivery, prosthetic valve 42 is compressed (e.g., crimped)such that all coupling tabs 220 are disposed in respective troughs 222.Prosthetic valve 42 and pushing member 140 b are disposed within thelumen of delivery tube 154. Delivery tube 154 restricts expansion ofprosthetic valve 42, thereby holding coupling tabs 220 in troughs 222,in the configuration described herein. Coupling tabs 220 restrictmovement of prosthetic valve 42 with respect to pushing member 140 b.Delivery tube 154 therefore facilitates coupling of prosthetic valve 42to pushing member 140 b via coupling tabs 220. As described withreference to FIGS. 62C-D, prosthetic valve 42 (or another medical device150) is advanced to the site of implantation, where pushing member 140 bpushes prosthetic valve 42 out of delivery tube 154. When coupling tabs220 emerge from delivery tube 154, expansion of prosthetic valve 42releases coupling tabs 220 from troughs 222, thereby releasingprosthetic valve 42 from the pushing member.

Reference is made to FIGS. 64A-C, which are schematic illustrations of alock 170 for facilitating delivery of a medical device, in accordancewith some applications of the invention.

Reference is now made to FIG. 64A. Lock 170 comprises a tubular member4172 and a plug 174. Plug 174 is dimensioned such that it is disposablein, and slidable through the lumen of tubular member 4172. Typically,plug 174 is dimensioned so as to fit tightly in the lumen of tubularmember 4172 in a manner in which an outer surface of plug 174 isdisposed very close to an inner surface to tubular member 4172, i.e.,such that little space exists between the plug and the tubular member.Plug 174 is shaped to define a trough 176. Trough 176 typically runsalong the surface of the plug from one end of the plug to a point alongthe length of the plug. Typically, trough 176 is shaped so as to definea widened part 178.

A coupling lead 4180 (e.g., a coupling wire) is disposable in trough176, and is reversibly couplable thereto (and thereby to lock 170), asdescribed hereinbelow. As is described hereinbelow, coupling lead 4180is coupled to a medical device 150 and facilitates (1) coupling ofmedical device 150 to a delivery mechanism during delivery of themedical device and (2) decoupling of medical device 150 from thedelivery mechanism following implantation of device 150. Typically, aregion at an end of coupling lead 4180 is shaped to define a stopper182, which is thicker than other regions of the coupling lead, and isconfigured to be disposable in widened part 178 of trough 176, typicallywhen tubular member 4172 surrounds plug 174. Alternatively, stopper 182may comprise a distinct component that is coupled to coupling lead 4180.Trough 176, coupling lead 4180, widened part 178, and stopper 182 aredimensioned such that when the coupling lead and the stopper aredisposed in trough 176, plug 174 remains disposable in, and slidablethrough, tubular member 4172. FIG. 64A shows trough 176 disposed withinthe lumen of tubular member 4172 such that lock 170 assumes a lockingconfiguration. In this locking configuration, coupling lead 4180 is heldin the trough by the inner surface of the tubular member. Tubular member4172 therefore facilitates coupling of coupling lead 4180 to plug 174.

Reference is now made to FIG. 64B. Plug 174 is slid distally throughtubular member 4172, such that lock 170 is in an open configuration.Typically, plug 174 is moved using control wire 175. In this openconfiguration, trough 176 and stopper 182 are exposed from the tubularmember (i.e., are outside the tubular member). Coupling lead 4180 andstopper 182 are shown in FIG. 64B as being disposed within trough 176,by way of illustration and not limitation, as a temporary configurationprior to disengaging wire 4180 and stopper 182 from trough 176(disengaging of wire 4180 and stopper 182 are described hereinbelow).

Reference is now made to FIG. 64C. In the open configuration, couplinglead 4180 (and stopper 182) are allowed to leave trough 176. Typically,coupling lead 4180 is released from trough 176 by moving the former withrespect to the latter (e.g., by applying a moving force to eithercoupling lead 4180, directly or indirectly, or by applying a movingforce to plug 174 away from wire 4180). In some applications of theinvention, at least a portion of coupling lead 4180 is configured suchthat it automatically moves out of the trough upon being exposed fromthe tubular member (e.g., the coupling lead comprises a shape-memorymaterial such as nitinol). In some applications of the invention, trough176 and widened part 178 are shaped to facilitate release of couplinglead 4180 from trough 176. For example, a distal edge of widened part178 may be sloped such that distal movement of coupling lead 4180facilitates the release.

Reference is made to FIGS. 65A-B, which are schematic illustrations ofsequential steps in lock 170 being used to facilitate the delivery of amedical device 150, the medical device embodied by prosthetic valvesupport 40, in accordance with some applications of the invention. FIG.65A shows a coupling lead 4180 (e.g., a coupling wire) extending from aholding member 4046 (e.g., a holding member 4046 a) to another holdingmember 4046 (e.g., a holding member 4046 b). For some applications,holding members 4046 comprise holding members 46, described hereinabovewith reference to FIGS. 1C-F. Coupling lead 4180 is coupled to medicaldevice 150. For example, coupling lead 4180 may loop around a part ofmedical device 150. Alternatively, coupling lead 4180 may weave throughat least a portion of medical device 150, as shown in FIG. 65A. At leastone holding member 4046 (e.g., holding member 4046 a) comprises lock 170at a distal end of holding member 4046. Holding member 4046 is shaped todefine a lumen and defines tubular member 4172 of lock 170. Holdingmember 4046 a is reversibly coupled to a first portion of coupling lead4180 (e.g., an end portion of wire 4180, as shown) via lock 170. Theremaining portions of wire 4180 are threaded through support 40, asshown, and extend through a lumen, of holding member 4046 b, as shown.Alternatively, a second portion of coupling lead 4180 is coupled to aportion of holding member 4046 b.

In the application of the invention illustrated in FIG. 65A, two holdingmembers 4046 a are coupled to coupling lead 4180 via respective locks170, and one holding member 4046 b is coupled to coupling lead 4180without a lock 170. That is, a first holding member 4046 a holds a firstend of wire 4180, and a second holding member 4046 a holds a second endof wire 4180. Portions of wire 4180 extending from the first and secondends thereof are threaded through respective portions of support 40 andextend through a lumen of holding member 4046 b, as shown.Alternatively, each holding member 4046 a is coupled to respective firstends of respective first and second coupling leads 4180. Respectiveportions of the first and second coupling leads 4180 extending from therespective first ends thereof are threaded through respective portionsof support 40, and extend through a lumen of holding member 4046 b.Alternatively, respective second portions of the first and secondcoupling leads 4180 are coupled to a portion of holding member 4046 b.

Reference is now made to FIG. 65B. At the site of implantation, lock 170is moved into its open configuration, thereby releasing coupling lead4180 from holding member 4046 a. Coupling lead 4180 is then decoupled(e.g., unthreaded or unlooped) from medical device 150 (e.g., by pullingon a portion of coupling lead 4180). In some applications of theinvention, holding member 4046 b is slidably coupled to coupling lead4180, and the decoupling of coupling lead 4180 from medical device 150is performed by withdrawing coupling lead 4180 proximally, throughholding member 4046 b. In other applications of the invention, holdingmember 4046 b is substantially attached to coupling lead 4180, and thedecoupling of coupling lead 4180 from medical device 150 is performed bywithdrawing holding members 4046 proximally following the decoupling ofholding members 4042 a from coupling lead 4180. Medical device 150 istypically left at the site of implantation following the decoupling.

Reference is made to FIGS. 66A-B, which are schematic illustrations ofsequential steps in lock 170 facilitating the delivery of a medicaldevice 150, the medical device embodied by prosthetic valve support 40,in accordance with some applications of the invention. Reference is nowmade to FIG. 66A. In this application of the invention, both ends ofeach coupling lead 4180 are coupled to one respective holding member4046. Each one of holding members 4046 comprises a respective lock 170.A respective coupling lead 4180 is coupled to each holding member 4046.For each holding member 4046, one end of coupling lead 4180 (i.e., theend of wire 4180 comprising stopper 182) is reversibly coupled to theholding member via lock 170, as described hereinabove with reference toFIG. 65A. The other end of the coupling lead is coupled to the holdingmember in a substantially fixed manner (e.g., attached to the holdingmember, or attached to a second part of lock, such as a second part ofplug 174). In such a manner, each coupling lead 4180 forms a loop arounda part of medical device 150 (as shown in the enlarged image of FIG.66A), thereby coupling each coupling lead 4180, and thereby couplingeach holding member 4046, to medical device 150.

Reference is now made to FIG. 66B. At the site of implantation, eachlock 170 is moved into its open configuration (described hereinabove),thereby releasing one end of each coupling lead 4180 (i.e., the end ofwire 4180 comprising stopper 182), and thereby opening the loop formedby coupling lead 4180. Each coupling lead 4180 is withdrawn proximally(i.e., by pulling proximally on each holding member 4046, as shown),thereby uncoupling (e.g., unthreading or unlooping) coupling lead 4180from medical device 150.

For some applications of the present invention, the other end ofcoupling lead 4180 is attached to a portion of holding member 4046. Insuch applications, withdrawal of coupling lead 4180 typically compriseswithdrawing holding member 4046 proximally.

For some applications of the invention, the other end of coupling lead4180 is attached to a portion (e.g., an outer surface of) of plug 174.For such applications, withdrawal of coupling lead 4180 may comprisewithdrawing the plug into tubular member 4172 (i.e., holding member4046).

In either application, following the decoupling of holding members 4046and wires 4180 from device 150, medical device 150 is typically left atthe site of implantation.

Reference is made to FIGS. 67A-B, which are schematic illustrations ofsequential steps in lock 170 facilitating the delivery of a medicaldevice 150, the medical device embodied by prosthetic valve support 40,in accordance with some applications of the invention. Reference is nowmade to FIG. 67A. One end of coupling lead 4180 (i.e., the end of wire4180 comprising stopper 182) is reversibly coupled to holding member4046 via lock 170, as described hereinabove with reference to FIG. 65A.The other end of the coupling lead is coupled to medical device 150 in asubstantially fixed manner. Typically, but not necessarily, couplinglead 4180 is short in comparison to the coupling lead described withreference to FIGS. 65A-B and 66A-B.

Reference is now made to FIG. 67B. At the site of implantation, lock 170is moved into its open configuration, releasing one end of coupling lead4180 (i.e., the end of wire 4180 comprising stopper 182). Holdingmembers 4046 are withdrawn proximally, releasing coupling lead 4180 andmedical device 150 from holding members 4046. Following the decouplingof holding members 4046 from device 150, medical device 150 is typicallyleft at the site of implantation. In this application of the invention,coupling leads 4180 typically remain coupled to medical device 150.

The applications of the invention described with reference to FIGS.64A-C, 65A-B, 66A-B, and 67A-B may be used in combination with eachother, and/or in combination with applications of the inventiondescribed herein, including those comprising delivery and/or deploymentof prosthetic valve 42, prosthetic valve support 40, and/or medicaldevice 150. These applications of the invention may also be used todeliver and/or deploy medical devices not described herein.

Reference is made to FIGS. 68A-B and 69A-E, which are schematicillustrations of prosthetic valve support 40 comprising a retrievabilityfunctionality, in accordance with some applications of the invention.

FIGS. 68A-B show prosthetic valve support 40 is coupled to one or moreholding members 4046 via one or more coupling retrieving wires 4180, inaccordance with respective applications of the invention. Typically,prosthetic valve support 40 is coupled to 2 or more (e.g., 3) holdingmembers 4046 via 2 or more (e.g., 3) coupling leads 4180. Typically, theends of each coupling lead 4180 are disposed within holding members4046, or more proximally (e.g., outside a body of the subject). Aportion (e.g., a middle portion) of each coupling lead is disposedthrough respective portions of prosthetic valve support 40 (e.g.,threaded through support 40), thereby coupling the prosthetic valvesupport to holding members 4046. Since (1) the respective ends ofcoupling leads 4180 are coupled to or extend beyond a proximal end ofholding members 4046, and (2) respective middle portions of wires 4180are threaded through respective portions of support 40, each couplinglead forms a loop. Typically, this middle portion of each coupling leadis disposed through a peripheral region (e.g., close to an outer edge69) of the prosthetic valve support.

FIGS. 68A-B show two configurations of coupling leads 4180, couplingholding members 4046 to prosthetic valve support 40, in accordance withrespective applications of the invention. For these applications of theinvention, three coupling leads 4180 (e.g., coupling wires) are used,and are illustrated as coupling leads 4180 a, 4180 b, and 4180 c, forclarity. Prosthetic valve support 40 is typically deployed in the atrium26 of the subject, e.g., as described with reference to FIGS. 1B-D.

FIG. 68A shows the middle portions of wires 4180 a-c forming respectivepulling loops (e.g., closed loops) around and threaded through support40. That is, a respective pulling force is applied annularly to theentire support 40 by each one of wires 4180 a-c.

FIG. 68B shows the middle portions of wires 4180 a-c threaded throughportions of support 40 in a manner in which the respective middleportions of wires 4180 a-c collectively form a pulling loop. That is, arespective pulling force is applied to respective portions of support 40(i.e., to respective thirds of support 40) corresponding to the portionsof support 40 through which the respective middle portions of wires 4180a-c are threaded.

Reference is now made to FIGS. 69A-E, which are schematic illustrationsof sequential steps in the retrieval of prosthetic valve support 40described hereinabove with reference to FIGS. 68A-B, in accordance withsome applications of the invention. Should it be required (e.g., forrepositioning of the prosthetic valve support, or abortion of theprocedure), the deployed prosthetic valve support may be retrieved intoovertube 44. FIG. 69A shows prosthetic valve support 40 in a fullydeployed configuration, still coupled to holding members 4046 viacoupling leads 4180. In this configuration, prosthetic valve support 40is typically flat, but may have a different shape (e.g., a saddleshape).

Reference is now made to FIG. 69B. A user moves coupling leads 4180proximally with respect to holding members 4046 and prosthetic valvesupport 40 (e.g., the user pulls coupling leads 4180 through holdingmembers 4046). Due to the configuration of coupling leads 4180 (asdescribed with reference to FIGS. 68A-B) the portion of each couplinglead that passes through the prosthetic valve support becomes shortened,thereby reducing a perimeter of the peripheral region (e.g. of outeredge 69) of prosthetic valve support 40, through which coupling leads4180 are disposed.

FIG. 69C shows the perimeter of outer edge 69 of prosthetic valvesupport 40 having been reduced further, thereby deforming prostheticvalve support toward a cylindrical shape, with outer edge 69 defining aproximal end of the further-reduced support 40. FIG. 69D shows thediameter of outer edge 69 having been reduced, such that the proximalend comprising outer edge 69 of prosthetic valve support 40 is slidableand disposable in overtube 44. As the user pulls coupling leads 4180,he/she pushes overtube 44 distally over successive portions of support40. FIG. 69E shows holding members 4046 and prosthetic valve support 40being moved proximally with respect to overtube 44 (e.g., the prostheticvalve support is moved proximally and/or the overtube is moveddistally). As overtube 44 slides over prosthetic valve support 40, itcompresses more distal portions of the prosthetic valve support, untilthe prosthetic valve support has been entirely retrieved into overtube44. Prosthetic valve support 40 may be redeployed or may be removed fromthe subject. Retrieval and/or deployment may be halted and/or reversedat any stage in the process described with reference to FIGS. 69A-E.

The applications of the invention described with reference to FIGS.68A-B and 69A-E may be used in combination with each other, and/or incombination with applications of the invention described herein,including those which include prosthetic valve support 40.

Reference is made to FIGS. 70A-C, which are schematic illustrations ofprosthetic valve 42, comprising tissue-engagement elements 62, inaccordance with some applications of the invention. In theseapplications of the invention, tissue-engagement elements 62 comprisevalve-anchoring elements 64, disposed at the distal end of prostheticvalve 42. Each valve-anchoring element 64 may comprise a loop-shapedvalve-anchoring element 200 or a stick-shaped valve-anchoring element202. Loop-shaped valve-anchoring elements 200 have a larger surface areawith which to grasp leaflets 82, and are hypothesized to be facilitatemore atraumatic advancement with respect to tissue than are stick-shapedvalve-anchoring elements 202. Stick-shaped valve-anchoring elements 202are hypothesized to more easily, be insertable between chordae tendineae80 (e.g., comb between chordae tendineae), than are loop-shapedvalve-anchoring elements 200.

Prosthetic valve 42 may be coupled to one or more valve-anchoringelements 64, comprising loop-shaped valve-anchoring elements 200,stick-shaped valve-anchoring elements 202, or a combination thereof, inorder to facilitate deployment of prosthetic valve 42 and coupling ofthe prosthetic valve to native heart valve 23. For example, stick-shapedvalve-anchoring elements 202 may be used in areas of heart valve 23 inwhich chordae tendineae 80 are disposed more densely, whereasloop-shaped valve-anchoring elements 200 may be used to capturerelatively exposed regions of leaflets 82. Loop-shaped valve-anchoringelements 200 and stick-shaped valve-anchoring elements 202 areillustrated here as fixed anchors. In some applications of theinvention, elements 200 and 202 may be alternatively or additionallyused as hinged anchors (e.g., hinged anchors 340) and/or clamping hingedanchors (e.g., clamping hinged anchors 350), as described hereinabove.

Reference is now made to FIG. 71, which is a schematic illustration ofprosthetic valve 42, for placing inside native heart valve 23 of thepatient, in accordance with some applications of the present invention.For this application of the invention, native valve 23 includes mitralvalve 24. The primary structural element 130 of the prosthetic valve hasa diameter d, and a corresponding cross-sectional area. The annulus ofthe native valve, which is typically saddle-shaped, defines an area A1,as shown. For some applications, area A1 is measured, e.g., using ameasuring ring prior to deployment of valve 42. Taking this measuringinto account, a suitably-sized prosthetic valve is chosen to be placedin the annulus, in a manner in which the cross-sectional area of theprosthetic valve in its deployed state is less than 90% (e.g., less than80%, or less than 60%) of area A1.

For some applications, diameter d of the prosthetic valve is less than25 mm, e.g., less than 20 mm, and/or more than 15 mm, e.g., 15-25 mm.For some applications, placing a prosthetic valve inside the nativevalve, with the dimensions of the native valve annulus and theprosthetic valve as described, facilitates sealing of the prostheticvalve with respect to the native valve, by the native valve leafletsclosing around the outer surface of the prosthetic valve. In suchapplications, prosthetic valve 42 is implanted directly within nativevalve 23 (i.e., without support 40).

For some applications, a prosthetic valve support 40, that is shaped todefine a lumen, is placed against the annulus of native valve 23 (e.g.,as described with reference to FIGS. 1A-H). The lumen of support 40 hasa cross-sectional area A2 that is less than 90% (e.g., less than 80%, orless than 60%) of area A1 of native valve 23. As described hereinabove,prosthetic valve 42 is typically coupled to prosthetic valve support 40and, thereby, to native valve 23, at least in part by expansion of theprosthetic valve such that primary structural element 130 exerts aradial force against inner edge 68 of prosthetic valve support 40. Thecross-sectional area defined by the primary structural element 130 ofthe prosthetic valve, upon expansion of the prosthetic valve, is limitedby the cross-sectional area A2 of the lumen of the prosthetic valvesupport 40 to less than 90% (e.g., less than 80%, or less than 60%) ofarea A1 of native valve 23. For some applications, placing a prostheticvalve support 40 at the native valve, as described, facilitates sealingof the prosthetic valve with respect to the native valve, by the nativevalve leaflets closing around the outer surface of the prosthetic valve.

Typically, placing a prosthetic valve inside the native valve with thedimensions of the native valve annulus, the prosthetic valve 42, and/orvalve support 40 as described in the above paragraphs, facilitatessealing of the prosthetic valve with respect to the native valve. Forsome applications, the sealing is facilitated by the native leafletsbeing pushed against, and closing against, the outer surface of theframe of the valve during systole, in a similar manner to the manner inwhich native valve leaflets coapt during systole, in a healthy mitralvalve.

Typically, as the diameter d of the prosthetic valve is increased, theproportion of the native leaflets that is pushed against the outersurface of the valve during systole is increased, thereby enhancing thesealing of the native leaflets with respect to the frame of theprosthetic valve. However, beyond a given diameter, as the diameter d ofthe prosthetic valve is increased, the native valve leaflets are pushedapart at the commissures, thereby causing retrograde leakage of bloodthrough the commissures. Therefore, in accordance with some applicationsof the present invention, prosthetic valve 42, and/or valve support 40are chosen such that the cross-sectional area of the prosthetic valve(when expanded inside the valve support) is less than 90% (e.g., lessthan 80%, or less than 60%) of area A1 of native valve 23. Thus, thevalve support facilitates additional sealing of the prosthetic valvewith respect to the native valve, by the native valve leaflets closingaround the outer surface of the prosthetic valve, while not causingretrograde leakage of blood through the commissures.

For some applications, in order to facilitate the sealing of the nativevalve around the outer surface of the prosthetic valve, a material isplaced on the outer surface of the prosthetic valve in order to providea sealing interface between the prosthetic valve and the native valve.For example, a smooth material that prevents tissue growth (e.g.,polytetrafluoroethylene (PTFE), and/or pericardium) may be placed on theouter surface of the prosthetic valve. Alternatively or additionally, amaterial that facilitates tissue growth (such as polyethyleneterephthalate; PET) may be placed on the outer surface of the prostheticvalve, in order to (a) act as a sealing interface between the nativevalve and the prosthetic valve, and (b) facilitate tissue growth aroundthe prosthetic valve to facilitate anchoring and/or sealing of theprosthetic valve.

Reference is made to FIGS. 72A-D, which are schematic illustrations ofan implant 2030, comprising a prosthetic valve support 2040, and aprosthetic valve 2042, in accordance with some applications of theinvention. Implant 2030 is configured to be implanted at a native heartvalve of a subject, such as the mitral valve 2024 of the subject.

FIG. 72A shows support 2040 and prosthetic valve 2042 of implant 2030 inrespective fully uncompressed configurations thereof. Support 2040comprises an upstream support portion 2041, which is shaped to define anopening 2045, and configured to be placed against an upstream side ofthe native valve of the subject (e.g., against an atrial side of themitral valve of the subject, such as against the annulus of the mitralvalve of the subject). Typically, upstream support portion 2041 isconfigured to be placed against the upstream side of the native valvesuch that the entire of opening 2045 is disposed above (i.e., upstreamand within a periphery defined by) the orifice of the native valve.Typically, upstream support portion 2041 is configured and/or selectedsuch that opening 2045 has a greatest diameter that is less than 90%(e.g., less than 80%, e.g., as less than 60%, such as less than 50%) ofa greatest diameter of the orifice of the native valve. Typically,upstream support portion 2041 is generally annular (e.g., portion 2041and opening 2045 are generally elliptical, circular, and/or oval).

In the fully uncompressed configuration thereof, upstream supportportion 2041 typically has an outer perimeter 2069 of length between 125and 190 mm (e.g., between 140 and 170 mm, such as between 140 and 150mm), and an inner perimeter 2068 (that defines opening 2045) of lengthbetween 62 and 105 mm (e.g., between 65 and 80 mm, such as between 75and 80 mm). When upstream support portion 2041 is annular, the upstreamsupport portion, in the fully uncompressed configuration thereof,typically has an outer diameter d10 (e.g., a greatest outer diameter) ofbetween 40 and 80 mm (e.g., between 40 and 70 mm, such as between 40 and60 mm), and an inner diameter d11 (e.g., a greatest inner diameter) ofbetween 20 and 35 mm (e.g., between 23 and 32 mm, such as between 25 and30 mm). That is, opening 2045 typically has a diameter of between 20 and35 mm (e.g., between 23 and 32 mm, such as between 25 and 30 mm).Typically, outer perimeter 2069 has a length that is at least 10% (e.g.,at least 50%, such as at least 80%) greater than inner perimeter 2068.

In the fully uncompressed configuration thereof, upstream supportportion 2041 is typically (but not necessarily) generally flat (e.g.,laminar, and/or planar). For some applications, in the fullyuncompressed configuration, portion 2041 assumes a frustoconical shape,typically arranged from the generally flat composition of the portion.Portion 2041 has a thickness of less than 5 mm, such as less than 2 mm.Opening 2045 has a depth (e.g., a height) d12 from an upstream side 2047of the upstream support portion to a downstream side 2049 of theupstream support portion. Depth d12 of opening 2045 is less than 5 mm,such as less than 2 mm. Typically, therefore, inner diameter d11 is morethan 4 times (e.g., more than 6 times, such as more than 10 times)greater than depth d12. That is, opening 2045 is more than 4 times(e.g., more than 6 times, such as more than 10 times) wider than it isdeep. Typically, in the fully uncompressed configuration, upstreamsupport portion 2041 has a total height of less than 10 mm (e.g., lessthan 5 mm, such as less than 2 mm).

Typically, inner perimeter 2068 comprises, or is defined by, a freeinner edge of upstream support portion 2041. That is, opening 2045resembles a hole cut out of a lamina (e.g., out of a disc). For someapplications, inner perimeter 2068 comprises, or is defined by, a curvedand/or folded inner edge of upstream support portion 2041. If the innerperimeter of upstream support portion 2041 comprises, or is defined by,a curved or folded edge, then a radius of curvature of the curved orfolded edge is typically less than 2.5 mm, such as less than 1 mm. Thatis, the curve or fold of the edge is generally sharp, such that whenviewed from within opening 2045, the curved or folded edge looksgenerally like a free edge.

It is to be noted that, for simplicity, upstream support portion 2041 isgenerally described herein in terms of symmetrical geometric shapes(e.g., ellipse and frustum), but that the upstream support portion mayassume a symmetrical or an unsymmetrical shape.

Prosthetic valve 2042 comprises a generally tubular (e.g., cylindrical)primary structural element 2130, shaped to define a lumen 2043therethrough, and at least one check valve element (not shown),configured to regulate blood flow through the prosthetic valve.Typically, the check valve element comprises one or more prostheticvalve leaflets, disposed in lumen 2043, and coupled (e.g., sutured) tothe primary structural element. For some applications of the invention,the check valve element comprises a ball, disc, or other check valvecomponent. For some applications of the invention, prosthetic valve 2042comprises a commercially-available stent-based prosthetic valve.

Prosthetic valve 2042 is configured to be placeable in opening 2045 ofsupport 2040, and couplable to the support by being expandable withinthis opening, e.g., as described in more detail hereinbelow. Typically,support 2040 comprises tissue-engaging elements (e.g., support-anchoringelements), such as those described herein (not shown in FIGS. 72A-D),and is couplable to the native valve, such that coupling of prostheticvalve 2042 to the support, couples the prosthetic valve to the nativevalve. For some applications, prosthetic valve 2042 comprisestissue-engaging elements (e.g., valve-anchoring elements), such as thosedescribed herein (not shown in FIGS. 72A-D), and is alternatively oradditionally directly couplable to the native valve.

In the fully uncompressed configuration thereof, prosthetic valve 2042typically has a perimeter 2051 of length between 62 and 110 mm (e.g.,between 70 and 90 mm, such as between 80 and 90 mm), and a height d14,(i.e., a length from an upstream end to a downstream end) of between 15and 40 mm (e.g., between 20 and 35 mm, such as between 25 and 25 mm).When structural element 2130 is cylindrical, prosthetic valve 2042, inthe fully uncompressed configuration thereof, typically has a diameterd13 of between 20 and 35 mm (e.g., between 25 and 35 mm, such as between25 and 30 mm). Typically, support 2040 and prosthetic valve 2042 areconfigured and/or selected (e.g., paired), such that perimeter 2051 isslightly (e.g., between 1 and 15 mm, such as between 1 and 7 mm) greaterthan perimeter 2068, and/or that diameter d13 is slightly (e.g., between1 and 5 mm, such as between 1 and 3 mm) greater than diameter d11.

In the respective fully uncompressed configurations thereof, height d14of prosthetic valve 2042 is typically at least 1.5 times greater (e.g.,at least 3 times greater, such as at least 5 times greater) than thetotal height of upstream support portion 2041.

Typically, support 2040 comprises a lattice structure which defines aplurality of struts 2120, typically in a repeating arrangement, and aplurality of voids between the struts. Typically, upstream supportportion 2041 comprises the lattice structure of support 2040. Typically,prosthetic valve 2042 comprises a lattice structure which defines aplurality of struts 2124, and a plurality of voids between the struts.Support 2040 and prosthetic valve 2042 typically have shape-memory(e.g., resilient, pseudoelastic and/or superelastic) properties.Typically, struts 2120 and/or struts 2124 comprise a shape-memory (e.g.,resilient, pseudoelastic and/or superelastic) material, such thatsupport 2040 and/or prosthetic valve 2042 are compressible when acompressive force is applied (e.g., prior to implantation), andre-expandable when the compressive force is removed (e.g., duringimplantation), as described hereinbelow. Non-limiting examples ofmaterials that the support (e.g., struts 2120) and/or prosthetic valve(e.g., struts 2124) may comprise include nickel-titanium (Nitinol),stainless steel, nickel cobalt, cobalt chrome, titanium, tantalum, andpalladium.

Typically, support 2040 and/or prosthetic valve 2042 are at least inpart covered with a covering 2440 (for clarity, covering 2440 is onlyshown on support 2040). Non-limiting examples of materials that covering2440 may comprise include polyethylene terephthalate (e.g., polyester),polytetrafluoroethylene (e.g., Teflon, ePTFE), and pericardial tissue.For some applications, covering 2440 comprises a fabric. Typically, athickness of the covering is less than 0.5 mm, such as less than 0.2 mm,e.g., less than 0.1 mm, or less than 0.05 mm. In FIG. 72A, struts 2120are shown in phantom, as they are covered by covering 2440.

For some applications of the invention, covering 2440 is configured tofacilitate blood flow through the prosthetic valve, e.g., to channelblood through lumen 2043 defined by prosthetic valve 2042, and/or toprevent leakage (1) between the prosthetic valve and support 2040,and/or (2) between implant 2030 and the native valve. For someapplications of the invention, the covering is configured to mask sharpand/or hard surfaces (e.g., metal surfaces, such as surfaces of struts2120 and/or 2124), and thereby to protect native tissues from beingdamaged by such surfaces. For some applications of the invention, thecovering is configured to facilitate (e.g., to enhance) coupling betweensupport 2040 and prosthetic valve 2042 (e.g., as described hereinbelow),such as by increasing friction. For some applications of the invention,the covering is configured to facilitate (e.g., to encourage) growth oftissue (e.g., fibrosis) over one or more components of implant 2030.

FIG. 72B shows support 2040 and prosthetic valve 2042 of implant 2030 inrespective compressed configurations thereof, typically for delivery tothe native valve. Typically, support 2040 and prosthetic valve 2042 aredelivered percutaneously (e.g., transcatheterally). Typically, thesupport and the valve component are delivered to the native valvetransluminally (e.g., transfemorally). For some applications, support2040 and prosthetic valve 2042 are delivered to the native valvetransatrially. For some applications, support 2040 and prosthetic valve2042 are delivered to the native valve transapically. In the compressedconfiguration thereof, upstream support portion 2041 is typicallygenerally cylindrical, and is typically delivered to a site that isupstream of the native valve of the subject (e.g., the left atrium,upstream of the mitral valve of the subject), such that a downstream(e.g., distal) end 2053 of the support has a perimeter 2068 b, which isa compressed inner perimeter 2068, and an upstream end 2055 of thesupport comprises perimeter 2069 b, which is a compressed outerperimeter 2069.

In the compressed configuration thereof, upstream support portion 2041typically has (e.g., perimeters 2068 b and 2069 b have) a perimeter oflength between 9 and 30 mm (e.g., between 15 and 25 mm, such as between18 and 22 mm), and a height d15 of between 11 and 30 mm (e.g., between15 and 30 mm, such as between 15 and 25 mm). When upstream supportportion 2041, in the compressed configuration thereof, is cylindrical,portion 2041 typically has a diameter of between 3 and 9 mm (e.g.,between 5 and 8 mm, such as between 6 and 7 mm).

In the compressed configuration thereof, prosthetic valve 2042 istypically generally cylindrical. Compression of the prosthetic valvetypically comprises inwardly-radial compression, such that the componentis narrower and taller in the compressed configuration than in the fullyuncompressed configuration thereof. In the compressed configurationthereof, prosthetic valve 2042 typically has a perimeter 2051 b (acompressed perimeter 2051) of between 9 and 30 mm (e.g., between 10 and20 mm, such as between 15 and 20 mm), and a height d16 of between 16 and41 mm (e.g., between 20 and 35 mm, such as between 20 and 30 mm). Whenprosthetic valve 2042, in the compressed configuration thereof, iscylindrical, prosthetic valve 2042 typically has a diameter of between 2and 9 mm (e.g., between 3 and 8 mm, such as between 3 and 6 mm).

Support 2040 (e.g., portion 2041) and prosthetic valve 2042 typicallyhave shape-memory properties, and are compressed (e.g., crimped) intotheir respective compressed configurations prior to (e.g., immediatelyprior to) the implantation procedure. Typically, the support andprosthetic valve are retained (e.g., ‘constrained’) in thisconfiguration by a constraining member, such as an overtube, a deliverytube, and/or other delivery apparatus. Support 2040 and prosthetic valve2042 are typically subsequently expanded (e.g., ‘deployed’) close to thesite of implantation by releasing the constraining (e.g., compressive)force (e.g., by removing the constraining member). That is, thecompressed configurations of prosthetic valve support 2040 (e.g., ofupstream support portion 2041) and prosthetic valve 2042, described withreference to FIG. 72B, typically comprise constrained compressedconfigurations, and the fully uncompressed configurations, describedwith reference to FIG. 72A, are unconstrained uncompressedconfigurations.

FIG. 72C shows an end-view of implant 2030, with prosthetic valve 2042coupled to prosthetic valve support 2040 by being disposed and expandedwithin opening 2045 (not shown in FIG. 72C) defined by portion 2041.FIG. 72C shows downstream side 2049 of support 2040, therefore struts2120 are shown in solid form. Typically, prosthetic valve 2042 isdelivered to opening 2045 in a constrained compressed configurationthereof (e.g., as described with reference to FIG. 72B), and expanded(e.g., released) in the opening, such that prosthetic valve 2042 appliesa radially-expansive force against inner perimeter 2068 of portion 2041.Typically, this radially-expansive force facilitates coupling ofprosthetic valve 2042 to portion 2041.

So as to provide the radially-expansive force, and as describedhereinabove, prosthetic valve 2042 and support 2040 (e.g., portion 2041)are typically configured and/or selected (e.g., paired) such thatperimeter 2051 of prosthetic valve 2042, in the fully uncompressedconfiguration thereof, is slightly greater than inner perimeter 2068 ofportion 2041. When prosthetic valve 2042 is expanded within opening2045, portion 2041 (e.g., inner perimeter 2068) thereby restricts thefull expansion of prosthetic valve 2042. Therefore, in the coupledconfiguration shown in FIG. 72C, a perimeter 2051 c of prosthetic valve2042 is typically smaller than perimeter 2051 of the prosthetic valve inthe fully uncompressed configuration thereof.

As described hereinabove (e.g., with reference to FIG. 72A), upstreamsupport portion 2041 is configured to be placed against an upstream sideof the native valve. As further discussed hereinbelow (e.g., withreference to FIG. 72K), it should be noted, that radial expansion ofprosthetic valve 2042 against inner perimeter 2068 of upstream supportportion 2041, thereby typically does not cause the prosthetic valvesupport to apply a radially-expansive force to the native valve.

For some applications, the prosthetic valve is couplable to the upstreamsupport portion at a continuum of positions along the axial length ofthe prosthetic valve. That is, a physician can couple the prostheticvalve to the support at a continuum of depths within the support. Forexample, in applications in which the prosthetic valve is configured tobe coupled to the upstream support portion solely by theradially-expansive force, the prosthetic valve may be coupled to theupstream support portion at a continuum of positions along the length ofthe prosthetic valve.

As described hereinabove, the lattice structures of prosthetic valve2042 and portion 2041 typically define a repeating arrangement ofstruts, e.g., a repeating arrangement of shapes. For some applications,and as shown in FIG. 72C, prosthetic valve 2042 and portion 2041comprise the same number of arrangement repeats. For some suchapplications, this matching number of repeats facilitates coupling ofprosthetic valve 2042 and portion 2041. For example, and as shown inFIG. 72C, a number of inwardly-protruding ridges 2057 of portion 2041protrude (e.g., interpose) within an equal number of correspondingcircumferential voids defined by the lattice structure of prostheticvalve 2042. These ridges facilitate coupling of support 2040 andprosthetic valve 2042, e.g., by inhibiting axial movement of theprosthetic valve through opening 2045 of upstream support portion 2041.

Typically, the arrangement of repeating circumferential voids defined bythe lattice structure of the prosthetic valve is repeated axially,thereby defining a prismatic (e.g., cylindrical) shape of the prostheticvalve. For some applications, the prosthetic valve is thereby couplableto the upstream support portion at a plurality of positions along theaxial length of the prosthetic valve. That is, a physician can couplethe prosthetic valve is couplable to the upstream support portion at aplurality of depths within the support. For example, in applications inwhich when a circumferential arrangement of voids is repeated four timesalong the axial length of the prosthetic valve, the prosthetic valve istypically couplable to the upstream support portion at four positionsalong the axial length of the prosthetic valve.

It is noted that, for some applications, the above descriptions ofprosthetic valve 2042 and support 2040 are applicable to (e.g., theapplications described above are combinable with) other embodiments ofprosthetic valves and prosthetic valve supports described herein.

FIG. 72D shows an end view of an implant 2030 a, comprising prostheticvalve 2042 coupled to a prosthetic valve support 2040 a. For someapplications of the invention, prosthetic valve support 2040 acomprises, and/or is analogous to, another prosthetic valve support(e.g., prosthetic valve support 2040) described herein, and implant 2030a comprises, and/or is analogous to, other implants (e.g., implant 2030)described herein. Prosthetic valve support 2040 a comprises an upstreamsupport portion 2041 a. For some applications of the invention, upstreamsupport portion 2041 a comprises, and/or is analogous to, other upstreamsupport portions described herein. Upstream support portion 2041 acomprises a plurality of inwardly-protruding barbs 2102, protruding frominner perimeter 2068 into opening 2045, such that, when prosthetic valve2042 is expanded within opening 2045, barbs 2102 protrude (e.g.,interpose) into voids defined by the lattice structure of prostheticvalve 2042. Similarly to the protrusion of ridges 2057 (described withreference to FIG. 72C) the protrusion of barbs 2102 further facilitatescoupling of prosthetic valve support 2040 a and prosthetic valve 2042.For some applications, barbs 2102 are disposed on (e.g., protrude from)ridges 2057. For some applications, barbs 2102 are disposed betweenridges 2057 (e.g., protrude from sites between ridges 2057).

Reference is made to FIG. 73, which is a schematic illustration of aprosthetic valve support 2040 b, in accordance with some applications ofthe invention. For some applications of the invention, prosthetic valvesupport 2040 b comprises, and/or is analogous to, other prosthetic valvesupports described herein. For some applications, prosthetic valvesupport 2040 b comprises prosthetic valve support 2040, describedhereinabove. Support 2040 b comprises upstream support portion 2041,coupled to one or more clips 2900, configured to be couplable to one ormore native leaflets 2082 of the native valve. For some applications ofthe invention, clips 2900 comprise tissue-engaging elements and/orsupport-anchoring elements (e.g., as described hereinabove). For someapplications, prosthetic valve support 2040 b alternatively oradditionally comprises other tissue-engaging elements. Typically,support 2040 b comprises two clips 2900, coupled to portion 2041 at ornear inner perimeter 2068. Typically, clips 2900 are disposed oppositeeach other.

Typically, clips 2900 are articulatably coupled to portion 2041. Thatis, typically, clips 2900 can move, at least in part, with respect toportion 2041. Typically, each clip 2900 is coupled to portion 2041 via aconnector 2540, which facilitates this movement. Typically, but notnecessarily, connector 2540 comprises a flexible material, such as afabric and/or polymer. For some applications, connector 2540 comprisesone or more hinge points, to facilitate the movement of the clips.

Each clip 2900 typically comprises two or more clip elements, such as aclip arm 2920 and a clip arm 2922, movable with respect to each other.Typically, the clip arms are articulatably-coupled at an articulationpoint 2921, and are movable with respect to each other by the relativeangular disposition of the clip arms being controllable. Typically, clip2900 is configured to be biased (e.g., pre-set, such as shape-set) to bein a closed configuration, such that arms 2920 and 2922 are relativelydisposed at a generally small angle (e.g., less than 45 degrees, such asless than 20 degrees, such as less than 5 degrees) to each other. Forsome applications, in the closed configuration of clip 2900, arms 2920and 2922 touch each other at a site that other than the articulationpoint. Each clip 2900 is configured to be couplable to a native leaflet2082 of the native valve by enveloping the native leaflet when the clipis in the open configuration thereof, and clipping the leaflet betweenthe clip arms when the clip subsequently moves toward the closedconfiguration thereof.

Typically, arm 2920 is substantially immobile, and arm 2922 is (1)biased to assume a first configuration, and (2) movable between thefirst configuration and another configuration. Typically, the firstconfiguration of arm 2922 is a closed configuration. Typically, theother configuration of arm 2922 is an open configuration, whereby aportion of arm 2922 that is furthest from articulation point 2921 isdisposed (1) further from arm 2920 than is the same portion in thefirst, closed configuration, and (2) further from arm 2920 than aportion of arm 2922 that is closest to the articulation point. That is,an angular disposition of arm 2922 to arm 2920 is greater when arm 2922is in the open configuration thereof, than when arm 2922 is in theclosed configuration thereof. When arm 2922 is in the closedconfiguration thereof, clip 2900 is in the closed configuration thereof.When arm 2922 is in the open configuration thereof, clip 2900 is in theopen configuration thereof. That is, clip 2900 is movable between openand closed configurations thereof, by arm 2922 moving between open andclosed configurations thereof. FIG. 73 shows detailed illustrations ofclip 2900 in the open and closed configurations, and further shows anexploded view of the components of clip 2900.

Clip 2900 further comprises a clip-controller interface, typicallycomprising a pull-wire 2924, which facilitates movement of arm 2922between the closed and open configurations, i.e., relative angularmovement of arms 2920 and 2922. Pull-wire 2924 is typically coupled toarm 2922, and controlled from outside the body of the subject. Forexample, pull-wire 2924 may be coupled to arm 2922, and extend to a clipcontroller (e.g., clip controller 2930, described with reference toFIGS. 74A-L) disposed within delivery apparatus, and ultimatelycontrolled by a physician. Typically, pull-wire 2924 is coupled to arm2922 such that (1) placing the pull-wire under tension (e.g., bypulling) moves arm 2922 toward the open configuration, and (2) releasingthe tension, at least in part, allows the arm to return toward theclosed configuration.

For some applications of the invention, both clips 2900 are controlledsimultaneously by a user (e.g., clips 2900 are configured to operatesimultaneously). For some applications, each clip 2900 is controllableindependently. For some applications, clip 2900 further comprises one ormore grips, such as teeth 2928, which facilitate the clamping ofleaflets 2082 when clip 2900 is closed. For some applications, clips2900 may alternatively or additionally be directly coupled to theprosthetic valve, and configured to couple the prosthetic valve directlyto the native valve.

Reference is made to FIGS. 74A-L, which are schematic illustrations ofsteps in the implantation of implant 2030 b, comprising prosthetic valve2042 and prosthetic valve support 2040 b, in a native heart valve, suchas mitral valve 2024 of a subject, in accordance with some applicationsof the invention.

Prosthetic valve support 2040 b is implanted using support-deliveryapparatus, such as support-delivery apparatus 2960. As describedhereinabove with reference to FIG. 73, each clip 2900 comprises aclip-controller interface, typically pull-wire 2924, which is configuredto open the clip when pulled (i.e., placed under tension). For someapplications of the invention, and as shown in FIG. 74A,support-delivery apparatus 2960 comprises at least one clip controller2930, one end of pull-wire 2924 is coupled to clip arm 2922, and anotherend of the pull-wire is coupled to controller 2930. Controller 2930comprises a tubular member 2172, shaped to define a lumen, and a plug2174. Plug 2174 is dimensioned such that it is disposable in, andslidable through (e.g., within, into, and out of) the lumen of tubularmember 2172. Plug 2174 comprises a restricting portion 2190 and a secondportion 2192.

Typically, at least part of plug 2174 (e.g., restricting portion 2190)is dimensioned so as to fit tightly in the lumen of tubular member 2172,in a manner in which an outer surface of plug 2174 (e.g., an outersurface of portion 2190) is disposed very close to an inner surface oftubular member 2172, i.e., such that little space exists between the atleast part of the plug and the tubular member. For example, the widestspace between portion 2190 and member 2172 may be smaller than athickness of pull-wire 2924. Typically, a surface of second portion 2192is disposed further from the inner surface of tubular member 2172, thanis the surface of the at least part of portion 2190.

Controller 2930 typically has at least three controller configurations,each configuration having a different relative disposition of plug 2174within tubular member 2172. In a first controller configuration, plug2174 is disposed at a first longitudinal position within tubular member2172. In a second controller configuration, the plug is disposed at asecond longitudinal position within the tubular member, the secondposition being more proximal (e.g., closer to a position outside thebody; typically upstream) than the first longitudinal position. In athird controller configuration, the plug is disposed at a thirdlongitudinal position, distal (e.g., downstream) to the firstlongitudinal position, such that at least restricting portion 2190 isdisposed outside of (e.g., distal to) the tubular member.

Controller 2930 has at least one locking configuration, in which (1) atleast part of restricting portion 2190 is disposed inside the lumen oftubular member 2172, and (2) pull-wire 2924, when coupled to thecontroller, is generally not decouplable from the controller. Typically,the first and second controller configurations, described hereinabove,are locking configurations. Controller 2930 further has at least oneopen configuration, in which (1) at least restricting portion 2190 isdisposed outside the lumen of tubular member 2172, and (2) pull-wire2924 is decouplable from the controller. Typically, the third controllerconfiguration, described hereinabove, is an open configuration.

Typically, and as shown in FIG. 74A, pull-wire 2924 comprises, and/or isshaped to define, a loop, and is coupled to controller 2930 by at leastpart of the loop being disposed against second portion 2192 when thelock is in, or moves into, a locking configuration thereof. For someapplications, pull-wire 2924 is generally flat (e.g., has an elongatetransverse cross-section, e.g., is a strip), is shaped to define a hole,and is coupled to controller 2930 by at least part of restrictingportion 2190 being disposed within the hole when the lock is in, ormoves into, a locking configuration thereof. Restricting portion 2190inhibits distal axial movement of the coupling lead, and tubular member2172 inhibits lateral movement of the coupling lead (e.g., the innersurface of the tubular member holds the coupling lead against secondportion 1192). Tubular member 2172 thereby facilitates coupling ofpull-wire 2924 to plug 2174, and thereby to controller 2930.

Controller 2930 is typically controlled (e.g., the configurations of thecontroller, such as the disposition of plug 2174 within tubular member2172, are typically selected), via a control rod 2175, using anextracorporeal controller, such as a control handle 2932, typicallydisposed at a proximal end of support-delivery apparatus 2960. Controlhandle 2932 comprises at least one adjuster 2934, each adjusterconfigured to control at least one clip 2900 of prosthetic valve support2040 b. Typically, control handle 2932 comprises two adjusters 2934,each adjuster configured to independently control one clip 2900. Forclarity, however, adjusters 2934 are shown operating simultaneously.Typically, but not necessarily, adjuster 2934 has pre-defined positionsin which it can reside, each pre-defined position of the adjustercorresponding to a respective configuration of controller 2930. That is,moving adjuster 2934 between the pre-defined positions thereof, movescontroller 2930 between the configurations thereof. For illustrativepurposes only, example pre-defined positions (A), (B) and (C) areindicated.

FIG. 74A shows support 2040 b having been delivered, usingsupport-delivery apparatus 2960, to left atrium 2026 of the heart of asubject (i.e., to a site upstream of native mitral valve 2024 of thesubject). Support 2040 b is typically delivered transcatheterally (e.g.,transvascularly, such as transfemorally), while in a compressedconfiguration thereof (e.g., as described with reference to FIG. 72B forsupport 2040). Typically, support 2040 b is delivered within an overtube2044, which provides a constraining (e.g., compressive) force, toconstrain the support in the compressed configuration thereof.Typically, upstream support portion 2041 of support 2040 b is coupled toa scaffold, such as a core 2946, and constrained in the compressedconfiguration by being disposed within an overtube 2044 of the deliveryapparatus. In the compressed configuration of support 2040 b, clips 2900are typically disposed downstream (e.g., distal) to the cylinder ofupstream support portion 2041, and coupled to core 2946.

During delivery of support 2040 b, and as shown in FIG. 74A, clips 2900are typically in the closed configuration thereof. FIG. 74A shows clips2900 exposed from the distal end of overtube 2044, overtube 2044 havingbeen retracted (e.g., overtube 2044 having been moved proximally, and/orsupport 2040 b having been moved distally). Adjuster 2934 of controlhandle 2932 is in a first position (A) (typically a middle position)thereof, and controller 2930 is in the first configuration thereof,whereby pull-wire 2924 is coupled to plug 2174, which is disposed withintubular member 2172.

FIG. 74B shows support 2040 b and core 2946 having been moved closer tothe native valve, and clips 2900 enveloping leaflets 2082 of the nativevalve. Adjuster 2934 of control handle 2932 is in a second position (B)thereof (typically more proximal than the first position), andcontroller 2930 is in the second configuration thereof. Movement ofcontroller 2930 into the second configuration thereof (i.e., moving plug2174 proximally) places pull-wire 2924 under tension (i.e., pulls thepull-wire), thereby pulling clip arm 2922, and opening clip 2900. Usingsupport-delivery apparatus 2960, the position of prosthetic valvesupport 2040 b is adjusted, so as to envelope native leaflets 2082between the clip arms of clips 2900.

FIG. 74C shows clips 2900, coupled (i.e., clipped) to native leaflets2082. The user (e.g., the physician) couples the clips to the nativeleaflets by closing the clips while the leaflets are enveloped by thearms of the clips. Adjuster 2394 of control handle 2932 is in firstposition (A) thereof (i.e., has been returned to first position (A)),and controller 2930 is in the first configuration thereof (i.e., hasbeen returned to the first configuration thereof). For some applicationsof the invention, control handle 2932 comprises a spring, whichfacilitates the return of adjuster 2394 to first position (A). Forexample, a user may apply a force to adjuster 2394 so as to move theadjuster to second position (B), and remove the force (e.g., release theadjuster) so as to return the adjuster to first position (A). Movementof controller 2930 into the first configuration thereof (i.e., movingplug 2174 distally) at least partly releases the tension on pull-wire2924, allowing the bias of clip 2900 (e.g., of clip arm 2922) to returnthe clip toward the closed configuration. If a native leaflet 2082 isenveloped by the clip arms, the leaflet is sandwiched between the arms,thereby coupling the clip to the leaflet.

For some applications, visualization (e.g., imaging) techniques such asultrasound are used to facilitate and/or confirm the coupling of clips2900 to leaflets 2082. For example, an echocardiogram may be used toobserve native leaflets 2082, and movement thereof. For someapplications, coupling of both native leaflets by clips 2900 isaccompanied by a generally lemniscate (e.g., ‘FIG. 8’) arrangement ofthe native leaflets, as shown in View A of FIG. 74C. Clips 2900 may berepeatedly opened and closed until coupling of the clips to leaflets2082 has been achieved.

For some applications of the invention, clips 2900 further comprise asecuring element (not shown), configured to secure the clips in theclosed configuration, following coupling of the clips to the nativeleaflets. For some applications of the invention, the securing elementis configured to secure the clips in one or a pre-defined selection ofclosed configurations (e.g., in a partially-closed configuration).

Reference is made to FIG. 74D. Following coupling of clips 2900 tonative leaflets 2082, the clips are released (e.g., decoupled) fromsupport-delivery apparatus 2960 (e.g., from core 2946) by decouplingpull-wire 2924 from controller 2930. To decouple the pull-wire from thecontroller, the user moves adjuster 2394 of control handle 2932 to thirdposition (C) thereof (typically a distal position), thereby movingcontroller 2930 in the third configuration thereof, whereby at leastrestricting portion 2190 of plug 2174 is disposed outside of tubularmember 2172. For some applications of the invention, control handle 2932comprises a safety device, such as a safety lock 2936, configured toprevent inadvertent movement of adjuster 2394 into position (C), andthereby inadvertent release of clips 2900. For such applications, safetylock is disabled (e.g., removed) prior to releasing clips 2900.

Movement of controller 2930 into the third position thereof (i.e.,moving at least part of plug 2174 outside of tubular member 2172) allowspull-wire 2924 to decouple from the controller. For some applications,pull-wire 2924 is configured to automatically decoupled from thecontroller when the controller moves into the third position. Forexample, the pull-wire may comprise a shape-memory (e.g., resilient,pseudoelastic and/or superelastic) material configured to lift the loopof the pull-wire away (e.g., laterally away) from plug 2174 whenrestricting portion 2190 moves outside of the tubular member.Non-limiting examples of materials that pull-wire 2924 may compriseinclude nickel-titanium (Nitinol), stainless steel, nickel cobalt,cobalt chrome, titanium, tantalum, palladium, polyester, PTFE, nylon,and cotton. For some applications of the invention, pull-wire 2924 isbiodegradable (e.g., bioabsorbent).

Reference is now made to FIG. 74E. Following the decoupling of clips2900 from controller 2930, upstream support portion 2041 of prostheticvalve support 2040 b is deployed (e.g., released from overtube 2044).Typically, overtube 2044 is withdrawn proximally, exposing successivelymore proximal (e.g., upstream) parts of portion 2041. As describedhereinabove (e.g., with reference to FIG. 72A), portion 2041 typicallycomprises a shape-memory material, and is compressed prior toimplantation. Portion 2041 thereby automatically expands upon removal ofthe constraining (e.g., compressive) force, i.e., when overtube 2044 iswithdrawn.

Immediately prior to the release of prosthetic valve support 2040 b fromthe overtube, the total length of overtube 2044 and support 2040 b maybe double or more than that of the overtube or support alone. For someapplications, this extra length can hinder the movement and/or removalof the overtube from the body of the subject. For some applications,overtube 2044 comprises a flexible and/or soft material, such as afabric or polymer, thereby becoming flexible as support 2040 b isremoved from within the overtube. It is hypothesized that thiscomposition/configuration of overtube 2044 facilitates deployment ofsupport 2040 b, and removal of the overtube from the body of thesubject.

FIG. 74F shows prosthetic valve support 2040 b during full deploymentthereof. Typically, and as described hereinabove, when upstream supportportion 2041 is delivered to the native valve in the cylindrical,compressed configuration, downstream (e.g., distal) end 2053 of thecylinder has perimeter 2068 b, which is a compressed inner perimeter2068. Distal end 2053, and therefore the inner perimeter of portion2041, is thereby coupled to the native valve before deploying (e.g.,expanding) upstream (e.g., proximal) end 2055, and therefore the outerperimeter of portion 2041. That is, the inner perimeter of portion 2041typically engages the native valve before the outer perimeter.

The two phases illustrated in FIG. 74F illustrate typical behavior ofupstream support portion 2041 during deployment thereof. As downstreamend 2053, moves out of overtube 2044, it expands toward becoming and/ordefining inner perimeter 2068 of portion 2041. As upstream end 2055moves out of overtube 2044, it expands to become outer perimeter 2069.Due to this arrangement, during deployment, upstream end 2055 typicallyexpands more than does downstream end 2053. For some applications,upstream end 2055 expands more than 1.5 times (e.g., more than twice) asmuch as does downstream end 2053.

Reference is now made to FIGS. 74G-H, which show support 2040 b in theimplanted configuration thereof. Upstream support portion 2041 isdescribed hereinabove (e.g., with reference to FIG. 72A) as beinggenerally flat when in its fully uncompressed configuration. However,portion 2041 is typically at least partly resilient. For example, asdescribed hereinabove, portion 2041 typically comprises a shape-memorymaterial. Implanting support 2040 b, as described with reference toFIGS. 74A-F, disposes portion 2041 against the upstream side of thenative valve (e.g., the upstream side of the native valve annulus).Typically, portion 2041 is held tightly against the upstream side of thenative valve by clips 2900, and deforms responsively to the contours ofthe native tissue (e.g., conforms to the native annulus), therebyassuming an implanted configuration. For some applications, portion 2041repeatedly deforms responsively to the contours of the native tissue, asthe native tissue repeatedly changes shape with the cardiac cycle.

Upstream support portion 2041 and clips 2900 are typically configuredsuch that, when support 2040 b is implanted at the native valve,upstream support portion inhibits downstream (e.g., ventricular)movement of support 2040 b, and clips 2900 inhibit upstream (e.g.,atrial) movement of the support. Typically, clips 2900 are configured tocouple the prosthetic valve support to the native valve such thatupstream support portion 2041 is in contact with the upstream side ofthe native valve (e.g., with the upstream side of the native annulus).For some applications, clips 2900 are the only component of prostheticvalve support 2040 b that inhibits upstream movement of prosthetic valvesupport.

The dimensions of upstream support portion 2041 in the implantedconfiguration thereof are typically similar to those of the same portionin the fully uncompressed configuration thereof, with any differencebetween the configurations typically due to the portion being implanted.For example, in some applications in which upstream support portion 2041is generally flat in the fully uncompressed (e.g., unconstraineduncompressed) configuration thereof, when support 2040 b is implanted atthe native valve, clips 2900 apply a downstream force to inner perimeter2068 of upstream support portion 2041, thereby inducing portion 2041 toassume a frustoconical shape in the implanted configuration thereof.When upstream support portion 2041 is generally frustoconical in theimplanted configuration thereof, a surface of portion 2041 typically hasan angle of less than 60 degrees (e.g., less than 45 degrees) from aplane of the smaller base of the frustum. (As shown in FIG. 74G, forexample, this angle is approximately 10 degrees.) That is, when upstreamsupport portion 2041 is generally frustoconical in the implantedconfiguration thereof, portion 2041 is closer to being planar than it isto being cylindrical. Alternatively, the surface of portion 2041 has anangle of greater than 60 degrees from the smaller base of the frustum.It is to be noted that, although upstream support portion 2041 isgenerally described herein in terms of symmetrical geometric shapes(e.g., ellipse and frustum), when conforming to native tissue, theupstream support portion may assume a symmetrical or an unsymmetricalshape.

Thus, in general, as shown in and described with reference to FIGS.72A-74L, (1) the fully uncompressed configurations of upstream supportportion 2041 described with reference to FIG. 72A are typicallyunconstrained uncompressed configurations, (2) the compressedconfigurations of portion 2041 described with reference to FIG. 72B aretypically constrained compressed configurations, and (3) the implantedconfigurations of portion 2041 described with reference to FIG. 74F aretypically constrained uncompressed configurations.

When implanted at the native valve, and thereby in the implantedconfiguration thereof, no part of upstream support portion 2041 isdisposed downstream of native leaflets 2082 (e.g., no part of portion2041 is disposed in ventricle 2028). Typically, when prosthetic valvesupport 2040 b is implanted at the native valve, no part of support 2040b that circumscribes a space (e.g., opening 2045) is disposed downstreamof the native leaflets. For some applications, when prosthetic valvesupport 2040 b is implanted at the native valve, no part of support 2040b that circumscribes a space is disposed downstream of the nativeannulus.

When implanted at the native valve, and thereby in the implantedconfiguration thereof, a height (i.e., a length along anupstream-to-downstream axis ax1 from a most upstream end to a mostdownstream end) of upstream support portion 2041, is typically less than20 mm (e.g., less than 10 mm, such as less than 5 mm). Typically, whenprosthetic valve support 2040 b is implanted at the native valve, nopart of the support that circumscribes a space has a height of more than20 mm. For some applications, when prosthetic valve support 2040 b isimplanted at the native valve, no part of the support that circumscribesa space has a height of more than 10 mm. For some applications, whenprosthetic valve support 2040 b is implanted at the native valve, nopart of the support that circumscribes a space has a height of more than5 mm.

As described hereinabove with reference to FIG. 73, clips 2900 arearticulatably-coupled to upstream support portion 41 of prosthetic valvesupport 2040 b. Following the implantation (e.g., delivery, coupling anddeployment) of prosthetic valve support 2040 b, clips 2900 can move, atleast in part, with respect to portion 2041, thereby allowing nativeleaflets 2082 to continue to function, at least in part. That is,implantation of prosthetic valve support 2040 b at a native valve, doesnot eliminate the native blood flow regulation functionality of thenative valve. FIGS. 74G-H show such movement of native leaflets 2082,and clips 2900. FIG. 74G shows support 2040 b implanted at mitral valve2024, with native leaflets 2082 open (e.g., during ventriculardiastole), clips 2900 having moved away from each other. FIG. 74H showssupport 2040 b implanted at mitral valve 2024, with native leaflets 2082closed (e.g., during ventricular systole), clips 2900 having movedtoward each other. Typically, each clip moves through an arc of greaterthan 45 degrees (e.g., greater than 60 degrees, such as greater than 80degrees) during each cardiac cycle.

FIGS. 74I-L show steps in the implantation of prosthetic valve 2042 inopening 2045 of prosthetic valve support 2040 b. As describedhereinabove, prosthetic valve 2042 is typically deliveredtranscatheterally. Typically, prosthetic valve 2042 is delivered to thenative valve from an upstream side (e.g., the atrial side of the mitralvalve), in a compressed configuration, and constrained within a deliverytube 2060, as shown in 31. The prosthetic valve and delivery tube aretypically placed within opening 2045. Delivery tube 2060 is thenwithdrawn from the prosthetic valve. Typically, the delivery tube iswithdrawn in a downstream direction (e.g., distally and/orventricularly), as shown in FIG. 74J. For some applications, thedelivery tube is withdrawn in an upstream direction (e.g., proximallyand/or atrially).

As regions of prosthetic valve 2042 are successively exposed as theyexit delivery tube 2060, they expand (e.g., radially). When deliverytube 2060 is withdrawn in the downstream direction, the upstream end ofthe prosthetic valve is exposed, and expands, thereby coupling theprosthetic valve to the upstream support portion of prosthetic valvesupport 2040 b, as shown in FIG. 74K (in which prosthetic valve 2042 isrepresented by a trapezoid/frustum). As described hereinabove (e.g.,with reference to FIG. 72C), for some applications, the prosthetic valveis couplable to the upstream support portion at a plurality of positionsalong the axial length of the prosthetic valve. For such applications, aphysician can typically implant (e.g., couple to support 2040 b) theprosthetic valve at a plurality of depths with respect to upstreamsupport portion 2041 and/or the native valve. For some suchapplications, the physician can implant the prosthetic valve prostheticvalve is implantable at a continuum of depths with respect to upstreamsupport portion 2041 and/or the native valve.

As shown in FIG. 74K, upstream support portion 2041 is placed againstthe upstream side of the native valve, and prosthetic valve 2042 isradially expanded within opening 2045 defined by the upstream supportportion. Radially-expansive force applied by prosthetic valve 2042 toupstream support portion 2041 (and which typically couples theprosthetic valve to the upstream support portion), is typically nottransferred to the native valve via the prosthetic valve support. Thatis, and as described hereinabove (e.g., with reference to FIGS. 72A and72C), radial expansion of prosthetic valve 2042 against inner perimeter2068 of upstream support portion 2041, typically does not cause theprosthetic valve support to apply a radially-expansive force to thenative valve.

Once delivery tube 2060 is fully withdrawn from prosthetic valve 2042,and the prosthetic valve is fully deployed (e.g., in the implantedconfiguration thereof), delivery tube 2060 is removed from the body ofthe subject. For some applications, when the delivery tube is withdrawnin the downstream direction (e.g., ventricularly), it is removed fromthe body via the lumen of the prosthetic valve, as shown in FIG. 74L.

As described hereinabove (e.g., with reference to FIGS. 73, and 74G-H),following the implantation (e.g., delivery, coupling and deployment) ofprosthetic valve support 2040 b, clips 2900 and native leaflets 2082 canmove, at least in part, thereby not eliminating the native blood flowregulation functionality of the native valve. In experiments conductedby the inventors, prosthetic valve support 2040 b has been implanted intwo pigs. Both animals remained alive and stable (e.g., had stable bloodpressure, pulse, breathing rate and oxygen saturation) for a duration ofsufficient length to withdraw the support-delivery apparatus, introducea valve-delivery system (e.g., delivery tube 2060), and deploy (e.g.,implant) prosthetic valve 2042 in opening 2045 of the support. Theperiod between implanting support 2040 b and implanting prosthetic valve2042 was between 5 and 10 minutes.

It is thereby hypothesized that, following implantation of prostheticvalve support 2040 b, the heart of the subject is able to continuepumping blood sufficiently to support the subject for longer than aminute, e.g., longer than 2 minutes, e.g., longer than 5 minutes, suchas longer than an hour. It is thereby hypothesized that a period ofgenerally normal physiological activity of the subject of up to aminute, e.g., up to 2 minutes, e.g., up to 5 minutes, such as up to anhour, between implantation of support 2040 b and implantation ofprosthetic valve 2042 (e.g., as described with reference to FIGS. 74I-Land/or 76D-E), is supported by prosthetic valve support 2040 b. It isthereby hypothesized that the implantation of implant 2030 b, comprisingsupport 2040 b and prosthetic valve 2042, may be performed without theuse of cardiopulmonary bypass. It is thereby hypothesized thatreplacement of a native valve with implant 2030 b, may be performed in ahuman, ‘off-pump,’ as was performed in the pig experiments.

Reference is again made to FIGS. 73 and 74A-L. It should be noted thatclips 2900, clip-controller interface (e.g., pull-wire 2924), clipcontroller 2930), and/or the support-delivery apparatus (e.g.,support-delivery apparatus 2960) are typically configured such that theclips are controllable independently of the deployment (e.g., expansion)of the prosthetic valve support (e.g., the withdrawal of overtube 2044from upstream support portion 2041). That is, clips 2900 are typicallyconfigured to be controllable independently of a state of deployment ofthe prosthetic valve support (e.g., prosthetic valve support 2040 b.Thus, a physician may independently control (1) the coupling (e.g.,‘clipping’) of clips 2900 to the leaflets of the native valve, and (2)the deployment of the prosthetic valve support (e.g., expansion of theupstream support portion).

Reference is made to FIGS. 75A-E, which are schematic illustrations ofimplant 2030 c, comprising prosthetic valve 2042 and prosthetic valvesupport 2040 c, and the implantation thereof, in accordance with someapplications of the invention. For some applications of the invention,prosthetic valve support 2040 c comprises, and/or is analogous to, otherprosthetic valve supports (e.g., prosthetic valve support 2040), andimplant 2030 c comprises, and/or is analogous to, other implants (e.g.,implant 2030) described herein. Support 2040 c comprises upstreamsupport portion 2041, coupled to one or more clips 2900, describedhereinabove (e.g., with reference to FIGS. 73 and 74A-L), and configuredto be couplable to one or more native leaflets 2082 of the native valve.Typically, support 2040 c comprises two clips 2900, coupled to portion2041 at or near inner perimeter 2068. Typically, clips 2900 are disposedopposite each other. Support 2040 c further comprises a stabilizingelement 3062 (e.g., a stabilizing strip or a stabilizing band), coupledto clips 2900.

Reference is now made to FIG. 75A, which shows a lower side view ofsupport 2040 c. Typically, stabilizing element 3062 is coupled to adownstream (e.g., distal) portion of clips 2900, and forms a ring shapedownstream (e.g., distal) to upstream support portion 2041. Stabilizingelement 3062 defines an opening 3064 (e.g., an aperture), and istypically inelastic and at least partly flexible. Non-limiting examplesof materials that element 3062 may comprise include polyester, PTFE(e.g., ePTFE), nylon, cotton, nitinol, stainless steel, nickel cobalt,cobalt chrome, titanium, tantalum and palladium. The flexibility ofelement 3062 typically facilitates the compressibility of the prostheticvalve support (e.g., for delivery) and/or movement (e.g., articulation)of clips 2900 with respect to upstream support portion 2041.

Stabilizing element 3062 is hypothesized to increase the stability ofprosthetic valve support 2040 c at the native valve. For example,element 3062 is hypothesized to at least partly inhibit lateral movement(e.g., rotation around an atrial-ventricular axis, e.g., ‘yaw’) of thesupport and/or clips, when the support is implanted at the native valve.Element 3062 is further hypothesized to reduce rolling movement (e.g.,movement around a lateral axis, e.g., an axis between two clips 2900,e.g., ‘pitch’ and ‘roll’) of implant 2030 c, including inversion (e.g.,‘flipping’) of the implant, following deployment (e.g., implantation) ofprosthetic valve 2042.

For some applications of the invention, stabilizing element 3062 isfurther hypothesized to stabilize clips 2900 during deployment of theelements, e.g., by facilitating coupling thereof to delivery apparatus,such as apparatus 2960.

FIGS. 75B-C show prosthetic valve support 2040 c, following implantationthereof at mitral valve 2024. As described hereinabove, the upstreamsupport portion is disposed upstream of the native valve. Stabilizingelement is disposed downstream of the native valve (i.e., in ventricle2028). Prosthetic valve support 2040 c is typically implanted asdescribed elsewhere herein for other prosthetic valve supports, mutatismutandis. As described hereinabove, stabilizing element 3062 istypically at least partly flexible, such that clips 2900 are movablewith respect to upstream support portion 2041. Typically, element 3062is sufficiently flexible to allow native leaflets 2082 to continue tofunction, at least in part. FIG. 75B shows support 2040 c implanted atmitral valve 2024, with native leaflets 2082 open (e.g., duringventricular diastole). FIG. 75C shows support 2040 c implanted at mitralvalve 2024, with native leaflets 2082 closed (e.g., during ventricularsystole). For some applications, when the native leaflets close,stabilizing element 3062 deforms toward a generally lemniscate (e.g.,‘figure-8’ or ‘butterfly’) configuration (e.g., as shown in FIG. 75C).

For some applications of the invention, a similar generally lemniscateconfiguration is formed by element 3062 when prosthetic valve support2040 c is coupled to delivery apparatus, during delivery to the nativevalve (e.g., as described for support 2040 b with reference to FIGS.74A-B). For some such applications, stabilizing element 3062 protrudesfrom the compressed prosthetic valve support, and facilitatespositioning and/or orientation of the support. For example, the ‘limbs’of the lemniscate are typically oriented at right angles to clips 2900,and protrude from the compressed support. When the clips are in closeproximity to the native leaflets, the ‘limbs’ are typically downstreamof the leaflets, and interact (e.g., touch) chordae tendineae of thenative valve. By orienting the prosthetic valve support such that the‘limbs’ have the least interaction with chordae tendineae (typicallywhen the limbs are oriented toward commissures of the native valve), auser automatically orients clips 2900 toward leaflets 2082 of the nativevalve.

Similarly to support 2040 b (described with reference to FIGS. 74A-L),implantation of prosthetic valve support 2040 c at a native valve doesnot eliminate the native blood flow regulation functionality of thenative valve. It is thereby hypothesized that, following implantation ofprosthetic valve support 2040 c, the heart of the subject is able tocontinue pumping blood sufficiently well to support the physiologicalsystems of the subject for longer than a minute, e.g., longer than 2minutes, e.g., longer than 5 minutes, such as longer than an hour. It isthereby hypothesized that a period of up to a minute, e.g., up to 2minutes, e.g., up to 5 minutes, such as up to an hour, betweenimplantation of support 2040 c and implantation of a prosthetic valve(e.g., prosthetic valve 2042), is supported by prosthetic valve support2040 c. It is thereby hypothesized that the implantation of implant 2030c, comprising support 2040 c and prosthetic valve 2042, may be performedwithout the use of cardiopulmonary bypass. That is, it is hypothesizedthat replacement of a native valve with implant 2030 c, may be performed‘off-pump’.

When implanted at the native valve, and thereby in the implantedconfiguration thereof, no part of stabilizing element 3062 is disposedupstream of native leaflets 2082 (e.g., no part of element 3062 isdisposed in atrium 2026). Typically, when prosthetic valve support 2040c is implanted at the native valve, no part of support 2040 c thatcircumscribes a space (e.g., portion 2041, which circumscribes opening2045 and/or element 3062, which circumscribes opening 3064) traverses(e.g., fully traverses) the native annulus.

When implanted at the native valve, and thereby in the implantedconfiguration thereof, a height (i.e., a length along anupstream-to-downstream axis ax2 from a most upstream part to a mostdownstream part) of stabilizing element 3062, is typically less than 20mm (e.g., less than 10 mm, such as less than 5 mm). For example,stabilizing element 3062 typically has a thickness of less than 20 mm(e.g., less than 10 mm, e.g., less than 5 mm, such as less than 1 mm).Typically, when prosthetic valve support 2040 c is implanted at thenative valve, no part of the support that circumscribes a space has aheight of more than 20 mm. For some applications, when prosthetic valvesupport 2040 c is implanted at the native valve, no part of the supportthat circumscribes a space has a height of more than 10 mm. For someapplications, when prosthetic valve support 2040 c is implanted at thenative valve, no part of the support that circumscribes a space has aheight of more than 5 mm.

FIG. 75D shows implant 2030, comprising prosthetic valve support 2040 cand prosthetic valve 2042, following implantation at mitral valve 2024.The prosthetic valve is typically implanted as described elsewhereherein (e.g., with reference to FIGS. 74I-L), mutatis mutandis.Prosthetic valve 2042 is deployed (e.g., delivered and expanded) inopening 2045, defined by upstream support portion 2041, and in opening3064, defined by stabilizing element 3062. That is, when prostheticvalve 2042 is deployed at the native valve, it is expanded such that (1)an upstream (e.g., proximal) portion of the prosthetic valve engages(e.g., couples to) inner perimeter 2068 of support 2040 c, and (2) adownstream (e.g., distal) portion of the prosthetic valve is disposedwithin the opening of the stabilizing element. For some applications ofthe invention, and as illustrated in FIG. 75D, the distal portion of theprosthetic valve engages (e.g., couples to) the stabilizing element.

For some applications of the invention, stabilizing element 3062 isconfigured (e.g., dimensioned) such that, when the prosthetic valve isexpanded within the opening of the stabilizing element, the stabilizingelement restricts the full expansion of the downstream portion of theprosthetic valve. That is, for some applications, upon expansion of theprosthetic valve, a transverse cross-sectional dimension (e.g., area)defined by a downstream portion of the prosthetic valve is determined(e.g., restricted) by a transverse cross-sectional dimension (e.g.,area) of opening 3064 of the stabilizing element. For some applications,one or more dimensions of opening 3064, defined by stabilizing element3062, are substantially equal to one or more dimensions of opening 2045,defined by upstream support portion 2041. For some such applications,the expansion of both the downstream and upstream portions of theprosthetic valve are restricted to substantially the same transversecross-sectional dimensions, thereby facilitating the primary structuralelement of the prosthetic valve to assume a generally prismatic (e.g.,generally cylindrical) shape.

For applications where stabilizing element 3062 limits the expansion ofprosthetic valve 2042, a radially-expansive force is thereby applied byprosthetic valve 2042 to stabilizing element 3062. Theradially-expansive force typically couples the prosthetic valve to thestabilizing element. That is, for some applications, prosthetic valve2042 is couplable to the stabilizing element. For some applications, theprosthetic valve is coupled to the stabilizing element by alternative oradditional means. For example, the stabilizing element may comprisebarbs and/or hooks, which facilitate coupling to the prosthetic valve.

For some applications of the invention, at least part (e.g., an innersurface) of stabilizing element 3062 comprises a friction coating thatis configured to increase friction and, thereby, coupling between thestabilizing element and the prosthetic valve.

For some applications of the invention, at least part of stabilizingelement 3062 is shaped to define ridges, which are configured (e.g.,dimensioned) to protrude (e.g., interpose) within corresponding voidsdefined by the lattice structure of the prosthetic valve. The ridgesfacilitate coupling of the stabilizing element to the prosthetic valve,e.g., by inhibiting axial movement of the prosthetic valve throughopening 3064.

For some applications of the invention, a soft (e.g., crushable)material is disposed on the inner surface of stabilizing element 3062(e.g., the stabilizing element comprises the soft material). Whenprosthetic valve 2042 expands, and applies radially-expansive force tothe stabilizing element, (1) the struts of the lattice structure of theprosthetic valve compress (e.g., crush) the parts of the soft materialagainst which the struts apply the force, and (2) the parts of the softmaterial that are disposed between the struts (i.e., that are disposedat voids defined by the lattice structure), form ridges that protrudebetween the struts (i.e., protrude into the voids). The protruding partsof the soft material facilitate coupling of the stabilizing element tothe prosthetic valve, e.g., by inhibiting axial movement of theprosthetic valve through opening 3064, such as by increasing friction.

For some applications of the invention, prosthetic valve 2042 (e.g., theprimary structural element of prosthetic valve 2042) is shaped to definea circumferential groove that is configured (e.g., dimensioned) toreceive stabilizing element 3062. That is, for some applications of theinvention, stabilizing element 3062 is configured (e.g., dimensioned) tobe placeable in a circumferential groove defined by prosthetic valve2042. When prosthetic valve 2042 is deployed, and expands within opening3064, element 3062 is disposed in the groove, thereby furtherfacilitating coupling of the stabilizing element to the prostheticvalve, e.g., by inhibiting axial movement of the prosthetic valvethrough the opening 3064.

Reference is made to FIGS. 76A-E, which are schematic illustrations ofsteps in the implantation of implant 2030 h, comprising prosthetic valve2042 and prosthetic valve support 2040 h, in a native heart valve, suchas mitral valve 2024 of a subject, in accordance with some applicationsof the invention. For some applications of the invention, prostheticvalve support 2040 h comprises, and/or is analogous to, other prostheticvalve supports described herein. Prosthetic valve support 2040 hcomprises upstream support portion 2041 and clips 2900, and typicallycomprises, and/or is analogous to prosthetic valve support 2040 b. FIGS.76A-E show steps in the transapical implantation of implant 2030 h.

FIG. 76A shows support 2040 h being delivered, using support-deliveryapparatus 2970, via the apex of the heart, to left ventricle 2028 of thesubject. During delivery, portion 2041 is disposed, in the compressedconfiguration thereof, within an overtube 2972 of the deliveryapparatus. Typically, portion 2041 is disposed within a delivery tube2976, which itself is disposed within the overtube.

FIG. 76B shows clips 2900 in the open configuration thereof, and coupledto a scaffold, such as core 2974. Clips 2900 are typically operated andcoupled to native leaflets 2082 as described hereinabove, mutatismutandis. Upstream support portion 2041 is advanced, in the compressedconfiguration thereof, such that upstream end 2055 is upstream ofdownstream end 2053. Upstream end 2055 of portion 2041 is advancedbetween native leaflets 2082. Typically, coupling clips 2900 to leaflets2082 automatically advances at least part of portion 2041 (e.g.,upstream end 2055) between the native leaflets. FIG. 76C shows clips2900 in the closed configuration thereof, coupled to native leaflets2082.

After clips 2900 have been coupled to native leaflets 2082, deliverytube 2976 is withdrawn distally (e.g., atrially) from upstream supportportion 2041, such that downstream end 2053 of portion 2041 is exposed,and expands to define inner perimeter 2068 as described hereinabove,mutatis mutandis. As successively more distal (e.g., upstream) parts ofportion 2041 are exposed as they exit delivery tube 2976, they expand(e.g., radially). When portion 2041 is sufficiently exposed from thedelivery tube (e.g., when upstream end 2055 is exposed from the deliverytube), upstream end 2055 expands to define outer perimeter 2068, asdescribed hereinabove, mutatis mutandis. As shown in FIG. 76D, support2040 h thereby assumes its implanted configuration, as describedhereinabove, whereby clips 2900 are coupled to the native leaflets, andupstream support portion 2041 is disposed against the upstream side ofthe native valve (e.g., the upstream side of the native valve annulus).Delivery tube 2976 is subsequently withdrawn from atrium 2026 viaopening 2045 of upstream support portion 2041, and support-deliveryapparatus 2970 (including delivery tube 2976) is withdrawn from the bodyof the subject.

FIG. 76E shows prosthetic valve 2042 being coupled to support 2040 h(i.e., implanted). Prosthetic valve 2042 is delivered transapically, toventricle 2028 of the subject. During delivery, prosthetic valve 2042 isdisposed, in a compressed configuration thereof, within a delivery tube2986 of the delivery apparatus. The delivery tube containing theprosthetic valve is disposed in opening 2045 of upstream support portion2041. The delivery tube is subsequently withdrawn proximally (e.g.,ventricularly) from prosthetic valve 2042, such that the upstream end ofthe prosthetic valve is exposed. As successively more proximal (e.g.,downstream) parts of prosthetic valve 2042 are exposed as they exitdelivery tube 2986, they expand (e.g., radially). When prosthetic valve2042 is sufficiently exposed from the delivery tube, the prostheticvalve engages inner perimeter 2068 of upstream support portion 2041 ofsupport 2040 h, and couples the prosthetic valve thereto, as describedhereinabove, mutatis mutandis.

Once prosthetic valve 2042 is completely exposed (e.g., deployed), theprosthetic valve thereby assumes its implanted configuration, asdescribed hereinabove. Support-delivery apparatus 2980 (includingdelivery tube 2986) is subsequently withdrawn from the body of thesubject.

Reference is made to FIGS. 77-80, which are schematic illustrations ofimplants, each comprising a prosthetic valve support and a prostheticvalve, implanted at native valves of a heart 2020 of a subject, inaccordance with some applications of the invention. FIGS. 77-80 are notintended to limit the scope of the invention, but to indicate someplacements of the implants with respect to the anatomy of the heartand/or native valve, and to illustrate commonalities between suchplacements. Other prosthetic valves and prosthetic valve supportsdescribed herein may be implanted at the native valves, as describedwith reference to FIGS. 77-80, mutatis mutandis.

FIG. 77 shows implant 2030 d, comprising a prosthetic valve support 2040d and a prosthetic valve 2042 d, implanted at mitral valve 2024 of heart2020 of a subject, in accordance with some applications of theinvention. For some applications of the invention, prosthetic valvesupport 2040 d comprises, and/or is analogous to, other prosthetic valvesupports described herein, and implant 2030 d comprises, and/or isanalogous to, other implants described herein. Implant 2030 d (e.g.,support 2040 d and prosthetic valve 2042 d) are configured (e.g.,dimensioned) to be implanted at mitral valve 2024. Implant 2030 d istypically implanted at mitral valve 2024 as described elsewhere herein(e.g., with reference to FIGS. 74A-L and/or 76A-E). An upstream supportportion 2041 d of support 2040 d is disposed against the upstream (i.e.,atrial) side of mitral valve 2024, and is coupled to the native valve,e.g., using clips or another support-anchoring element. Prosthetic valve2042 d is disposed and expanded in the opening defined by portion 2041d, thereby traversing the annulus of the native valve.

FIG. 78 shows implant 2030 e, comprising a prosthetic valve support 2040e and a prosthetic valve 2042 e, implanted at tricuspid valve 2010 ofheart 2020 of a subject, in accordance with some applications of theinvention. For some applications of the invention, prosthetic valvesupport 2040 e comprise, and/or is analogous to, other prosthetic valvesupports described herein, and implant 2030 e comprises, and/or isanalogous to, other implants described herein. Implant 2030 e (e.g.,support 2040 e and prosthetic valve 2042 e) are configured (e.g.,dimensioned) to be implanted at tricuspid valve 2010. For example, andas shown in FIG. 78, an upstream support portion 2041 e of support 2040e typically defines a concavity 2121, configured to be oriented towardthe atrioventricular (AV) node, so as to reduce a likelihood of support2040 e interfering with electrical activity of the heart. Upstreamsupport portion 2041 e of support 2040 e is disposed against theupstream (i.e., atrial) side of tricuspid valve 2010, and is coupled tothe native valve, e.g., using clips or another support-anchoringelement. Prosthetic valve 2042 e is disposed and expanded in the openingdefined by portion 2041 e, thereby traversing the annulus of the nativevalve.

FIG. 79 shows implant 2030 f, comprising a prosthetic valve support 2040f and a prosthetic valve 2042 f, implanted at pulmonary valve 2012 ofheart 2020 of a subject, in accordance with some applications of theinvention. For some applications of the invention, prosthetic valvesupport 2040 f comprises, and/or is analogous to, other prosthetic valvesupports described herein, and implant 2030 f comprises, and/or isanalogous to, other implants described herein. Implant 2030 f (e.g.,support 2040 f and prosthetic valve 20421) are configured (e.g.,dimensioned) to be implanted at pulmonary valve 2012. For example, andas shown in FIG. 79, an outer perimeter of upstream support portion 2041f of support 2040 f may be dimensioned to be small enough to fit withinthe downstream portion of right ventricle 2013, but large enough toinhibit movement of implant 2030 f downstream through the pulmonaryvalve. Upstream support portion 2041 f of support 2040 f is disposedagainst the upstream (i.e., ventricular) side of pulmonary valve 2012,and is coupled to the native valve, e.g., using clips or anothersupport-anchoring element. Prosthetic valve 2042 f is disposed andexpanded in the opening defined by portion 2041 f, thereby traversingthe annulus of the native valve.

FIG. 80 shows implant 2030 g, comprising a prosthetic valve support 2040g and a prosthetic valve 2042 g, implanted at aortic valve 2014 of heart2020 of a subject, in accordance with some applications of theinvention. For some applications of the invention, prosthetic valvesupport 2040 g comprises, and/or is analogous to, other prosthetic valvesupports described herein, and implant 2030 g comprises, and/or isanalogous to, other implants described herein. Implant 2030 g (e.g.,support 2040 g and prosthetic valve 2042 g) are configured (e.g.,dimensioned) to be implanted at aortic valve 2014. For example, and asshown in FIG. 80, an outer perimeter of upstream support portion 2041 gof support 2040 g may be dimensioned to be sufficiently large to inhibitmovement of implant 2030 g downstream through the aortic valve, and/orprosthetic valve 2042 g, and prosthetic valve 2042 g may be dimensionedto reduce a likelihood of interference with (e.g., reduction of) bloodflow into the coronary arteries of the subject. Upstream support portion2041 g of support 2040 g is disposed against the upstream (i.e.,ventricular) side of aortic valve 2014, and is coupled to the nativevalve, e.g., using clips or another support-anchoring element.Prosthetic valve 2042 g is disposed and expanded in the opening definedby portion 2041 g, thereby traversing the annulus of the native valve.

Reference is again made to FIGS. 77-80. It is thereby to be noted thatalthough some apparatus and methods are described herein to facilitatereplacement of a native mitral valve of the subject, apparatus (andsubcomponents thereof) and methods described herein may also be used toreplace a native cardiac valve other than the native mitral valve, suchas the tricuspid valve, the aortic valve, and the pulmonary valve.

Reference is again made to FIGS. 1A-80. For each of the prosthetic valvesupports described, at least a part of the prosthetic valve supportcircumscribes (e.g., encloses on all lateral sides) a space. Forexample, the upstream support portions and stabilizing elementsdescribed hereinabove, define respective openings (e.g., apertures).These openings are thereby spaces that the upstream support portions andstabilizing elements circumscribe.

For some applications of the invention, following implantation at thenative valve, no part of the prosthetic valve support that circumscribesa space, traverses the native leaflets and/or annulus. For example,following implantation, the upstream support portions describedhereinabove (e.g., upstream support portions 41 and 2041) are typicallydisposed only upstream of the native leaflets and/or annulus. Similarly,for applications in which the prosthetic valve support comprises astabilizing element (e.g., stabilizing element 1062 or 3062), followingimplantation, the stabilizing element is typically disposed onlydownstream to the native leaflets and/or annulus. It is hypothesizedthat this advantageously facilitates continued function of the nativeleaflets following implantation of the prosthetic valve support, andprior to the implantation of a prosthetic valve, as describedhereinabove.

Typically, the perimeter (e.g., the circumference) of the spaces definedby the upstream support portions and stabilizing elements describedhereinabove, is greater than 60 mm. Typically, the upstream supportportions and stabilizing elements have respective heights of less than10 mm. For some applications of the invention, no part of the prostheticvalve support that circumscribes a space that has a perimeter that isgreater than 60 mm, has a height (e.g., a depth) that is greater than 10mm. For example, prosthetic valve supports that do not comprise acylindrical element (e.g., cylindrical element 90 or 690), do notcomprise a part that (1) circumscribes a space that has a perimeter thatis greater than 60 mm, and (2) has a height (e.g., a depth) that isgreater than 10 mm.

Reference is again made to FIGS. 1A-80. It is to be noted that theapparatus and techniques described hereinabove are not limited to thecombinations described hereinabove. For example:

(1) Any of the prosthetic valves described hereinabove (includingfeatures and/or components thereof) may be used in combination with anyof the prosthetic valve supports (including features and/or componentsthereof) described hereinabove (e.g., any of the prosthetic valvesupports described hereinabove may be used to facilitate implantation ofany of the prosthetic valves described hereinabove), mutatis mutandis;

(2) any of the prosthetic valve supports described hereinabove maycomprise any of the upstream support portions, tissue-engaging elements(e.g., support-anchoring elements and/or clips), connectors (e.g.,flexible and/or length-adjustable connectors), holding wires and/orstabilizing elements described hereinabove, mutatis mutandis;

(3) any of the prosthetic valves or prosthetic valve supports describedhereinabove may comprise any of the coupling functionalities (e.g.,barbs, coupling leads and/or support-engaging elements) describedhereinabove, for coupling a prosthetic valve support (e.g.,support-anchoring elements thereof) to a prosthetic valve, mutatismutandis;

(4) any of the tissue-engaging elements, and/or elements thereof,described hereinabove may be used in combination with any one ofprosthetic valve supports or prosthetic valves described herein, mutatismutandis. For example, tissue-engaging elements (e.g., support-anchoringelements) that are described hereinabove for coupling a prosthetic valvesupport to the native valve, may be alternatively or additionally usedto couple a prosthetic valve to the native valve (the tissue-engagingelement thereby acting as a valve-anchoring element), mutatis mutandis.Similarly, tissue-engaging elements (e.g., valve-anchoring elements)that are described hereinabove for coupling a prosthetic valve to thenative valve, may be alternatively or additionally used to couple aprosthetic valve support to the native valve (the tissue-engagingelement thereby acting as a support-anchoring element), mutatismutandis;

(5) any of the implantation techniques described hereinabove (e.g.,those described with reference to FIGS. 1A-H, 15A-E, 16, 28A-30B, 37A-H,38A-H, 50, 74A-L, 75A-D and 76A-F) may be used in combination with anyof the implants (e.g., any of the prosthetic valves and/or prostheticvalve supports) described hereinabove, mutatis mutandis;

(6) any of the delivery apparatus described hereinabove (e.g., thosedescribed with reference to FIGS. 9A-E, 27A-D, 31A-33C, 37A-H, 38A-H,62A-D, 63A-B, 64A-67B and 74A-L) may be used to facilitate delivery ofany of the implants (e.g., any of the prosthetic valves and/orprosthetic valve supports) described hereinabove, mutatis mutandis; and

(7) any of the techniques and apparatus described hereinabove (e.g.,those described with reference to FIGS. 9A-F, 25A-E, 27A-D, and68A-69E), for retrieval of a prosthetic valve or prosthetic valvesupport, may be used in combination with (e.g., may be used to retrieve)any of the prosthetic valves and/or prosthetic valve supports describedhereinabove, mutatis mutandis.

Reference is again made to FIGS. 1A-80. It is to be noted that for someapplications of the present invention that comprise tissue-engagingelements 62, movement of tissue-engaging elements 62 from theirconstrained configuration to their unconstrained configuration duringdeployment, comprises movement of over 180 degrees. For someapplications, tissue-engaging elements, comprising valve-anchoringelements, move from a constrained configuration distal to the primarystructural element of the prosthetic valve, to an unconstrainedconfiguration wherein a portion of each valve-anchoring element isdisposed inside the generally-cylindrical structure of the primarystructural element of the prosthetic valve (e.g., valve-anchoringelements protrude through voids defined by the lattice structure of theprimary structural element).

Reference is again made to FIGS. 1A-80. For some applications of theinvention, apparatus such as the prosthetic valves and/or prostheticvalve supports described hereinabove (e.g., the primary structuralelements, upstream support portions, and tissue-engaging elementsthereof), are covered at least in part with a covering. The covering maycomprise polyethylene terephthalate (e.g., polyester),polytetrafluoroethylene (e.g., Teflon, ePTFE), a fabric, and/or orpericardial tissue. Typically, a thickness of the covering is less than0.2 mm, e.g., less than 0.1 mm, or less than 0.05 mm. The covering maybe selected according to requirements. For example, for someapplications, a surface of the apparatus that is placed in contact withthe native valve is covered; the covering being configured to facilitatecoupling of the prosthetic valve support to the native valve, byenhancing tissue growth at the interface between the prosthetic valvesupport and the native valve. Conversely, for some applications, thecovering may be configured to inhibit tissue growth thereon. For someapplications, a surface of the apparatus is covered with the covering soas to inhibit (e.g., prevent) leakage of blood between the prostheticvalve and the native valve, and/or between the prosthetic valve and theprosthetic valve support.

For some applications, the prosthetic valve support (e.g., the upstreamsupport portion thereof) is not covered with the covering, and isconfigured to allow flow of blood therethrough. For example, theprosthetic valve support may be configured to allow flow of bloodthrough the interface between the valve support and the prostheticvalve, in order to accommodate antegrade flow of blood between thesubject's atrium and the subject's ventricle that is greater than can beaccommodated by blood flowing through the prosthetic valve alone. Forsome such application of the invention, the prosthetic valve support isnot covered with the covering and is configured to support prostheticvalve, such that the leaflets of the native valve (1) move in responseto the beating of the heart, (2) coapt with each other and/or with theprimary structural element of the prosthetic valve, and (3) inhibit(e.g., prevent) retrograde flow of blood through the prosthetic valvesupport.

Reference is yet again made to FIGS. 1A-80. It is to be noted thatalthough some apparatus and methods are described herein to replace anative heart valve (e.g., a native mitral valve) of the subject,apparatus (and subcomponents thereof) and methods described herein mayalso be used at any other site in the body of the subject. For example,delivery apparatus and/or locks described herein may be used tofacilitate implantation and/or adjustment of any suitable implant at agiven implantation site of a body of the subject, e.g., the stomach.

Reference is made to FIGS. 1A-80. It is to be noted that for someapplications of the present invention, medical device 150 comprises animplant that comprises a prosthetic valve support and a prostheticvalve. For other applications, medical device 150 comprises a prostheticvalve support. For yet other applications, medical device 150 comprisesa prosthetic valve.

Reference is again made to FIGS. 1A-80. It is to be noted that at leastsome of the tissue-engaging elements that are described herein asadjustable (e.g., length-adjustable), may be adjusted prior toimplantation, during the implantation procedure, or followingimplantation.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1-25. (canceled)
 26. Apparatus for use with a prosthetic heart valve at a native valve of a heart of a subject, the apparatus comprising: an adjustable-lumen prosthetic valve support, the prosthetic valve support having: a delivery state, in which the prosthetic valve support is transluminally deliverable to the heart; and an implantation state, into which the prosthetic valve support is transitionable within the heart, for implantation at the native valve, wherein: in the implantation state, the prosthetic valve support has an inner edge that defines a lumen through the prosthetic valve support, the lumen having a first diameter, after the prosthetic valve support is implanted at the native valve, the prosthetic valve support is transitionable into an enlarged state in which the lumen has a second diameter that is greater than the first diameter, and in the enlarged state, the prosthetic valve support is configured to support, at the native valve, the prosthetic heart valve within the lumen.
 27. The apparatus according to claim 26, further comprising: a tightening wire forming a loop around a central portion of the prosthetic valve support, and a spool, the spool coupled to the tightening wire; wherein the spool is configured to transition the lumen between the first and second diameters by adjusting the tightening wire.
 28. The apparatus according to claim 26, wherein the prosthetic valve support further comprises a plurality of tissue-engaging elements, the tissue-engaging elements being configured to engage tissue of the heart.
 29. The apparatus according to claim 28, wherein the tissue-engaging elements comprise support-anchoring elements, the support-anchoring elements being configured to anchor the prosthetic valve support to the native valve.
 30. The apparatus according to claim 29, wherein the support-anchoring elements are configured to anchor the prosthetic valve support to the native valve by coupling the prosthetic valve support to leaflets of the native valve.
 31. The apparatus according to claim 30, wherein, the support-anchoring elements are configured such that, while coupling the prosthetic valve support to leaflets of the native valve, the support-anchoring elements allow the leaflets to continue to function at least in part.
 32. The apparatus according to claim 26, wherein the prosthetic valve support comprises a frame, the frame: having a lattice structure, and defining, in the enlarged state, a generally annular shape.
 33. The apparatus according to claim 32, wherein: the prosthetic valve support further comprises a covering that covers at least a portion of the frame, and the covering is configured such that, while the prosthetic valve support supports the prosthetic heart valve at the native valve, the covering directs blood to flow through the prosthetic valve.
 34. The apparatus according to claim 33, wherein the covering is configured to facilitate coupling of the prosthetic valve support to the native valve.
 35. The apparatus according to claim 32, wherein the prosthetic valve support comprises a weak zone, the weak zone circumscribing the lumen defined by the prosthetic valve support.
 36. The apparatus according to claim 35, wherein the prosthetic valve support comprises a stretchable reinforcing-wire disposed near an inner edge of the prosthetic valve support.
 37. The apparatus according to claim 35, wherein a breakable reinforcing-wire is disposed near an inner edge of the prosthetic valve support.
 38. The apparatus according to claim 35, wherein the lattice structure does not extend into the weak zone.
 39. The apparatus according to claim 35, wherein the lattice structure of the frame outside the weak zone differs from the lattice structure of the frame within the weak zone.
 40. The apparatus according to claim 26, further comprising an expanding device, deliverable to the prosthetic valve support at the native valve, and configured to transition the prosthetic valve support from the implantation state to the enlarged state by expanding while disposed within the lumen of the prosthetic valve support, such that the expanding device applies a radially-expansive force from within the prosthetic valve support.
 41. The apparatus according to claim 40 wherein the expanding device comprises a balloon, the balloon being inflatable.
 42. The apparatus according to claim 40, wherein the expanding device is shaped to define a lumen.
 43. The apparatus according to claim 42, wherein the expanding device: comprises one or more temporary prosthetic valve leaflets disposed within the lumen of the expanding device, and is configured to facilitate continued blood flow through the prosthetic valve support via the lumen of the expanding device while the expanding device is expanded within the lumen of the prosthetic valve support.
 44. A method for treating a native valve of a heart of a subject, the method comprising: transluminally advancing, in a delivery state, an adjustable-lumen prosthetic valve support; delivering the prosthetic valve support to the heart while the prosthetic valve support is in the delivery state; transitioning, within the heart, the prosthetic valve support from the delivery state to an implantation state in which the prosthetic valve support has an inner edge that defines, through the prosthetic valve support, a lumen that has a first diameter; subsequently, coupling the prosthetic valve support to the native valve; subsequently, transitioning the prosthetic valve support from the implantation state to an enlarged state by enlarging the lumen such that the lumen has a second diameter that is greater than the first diameter; while the prosthetic valve support remains in the enlarged state, implanting a prosthetic heart valve by coupling the prosthetic heart valve to the prosthetic valve support such that the prosthetic valve support supports the prosthetic heart valve within the lumen of the prosthetic valve support.
 45. The method according to claim 44, wherein delivering the prosthetic valve support comprises: exerting a pushing force upon the prosthetic valve support to advance the prosthetic valve support within an overtube, and exposing the prosthetic valve support from a distal end of the overtube.
 46. The method according to claim 44, wherein the prosthetic valve support further includes: a tightening wire, the tightening wire forming a loop around a central portion of the prosthetic valve support, and a spool, the spool coupled to the tightening wire; and wherein transitioning the prosthetic valve support from the implantation state to the enlarged state comprises interacting with the spool to loosen the tightening wire.
 47. The method according to claim 44, wherein coupling the prosthetic valve support to the native valve comprises aligning the lumen of the support with an orifice of the native valve.
 48. The method according to claim 44, wherein the prosthetic valve support further includes tissue-engaging elements, the method further comprising engaging tissue of the native valve with the tissue-engaging elements.
 49. The method according to claim 48, wherein the tissue-engaging elements include support-anchoring elements, and engaging tissue of the native valve comprises anchoring the prosthetic valve support to the native valve by coupling the prosthetic valve support to leaflets of the native valve.
 50. The method according to claim 49, wherein coupling the prosthetic valve support to leaflets of the native valve comprises allowing the leaflets of the native valve to continue to function at least in part.
 51. The method according to claim 44, wherein transitioning the prosthetic valve support from the implantation state to the enlarged state comprises: advancing an expanding device to the prosthetic valve support at the native valve; expanding the expanding device while the expanding device is disposed within the lumen of the prosthetic valve support; and applying a radially-expansive force to an interior of the prosthetic valve support from within the prosthetic valve support.
 52. The method according to claim 51, further comprising removing the expanding-device from the subject.
 53. The method according to claim 51, wherein the prosthetic valve support further comprises a weak zone that circumscribes the lumen, and expanding the expanding-device comprises deforming the weak zone.
 54. The method according to claim 51, wherein the expanding device includes a balloon, and expanding the expanding-device within the lumen of the prosthetic valve support comprises inflating the balloon while the balloon is disposed within the lumen of the prosthetic valve support, the balloon shaped to define a lumen.
 55. The method according to claim 54, wherein the balloon further includes temporary prosthetic valve leaflets disposed within the lumen of the balloon, the method further comprising, prior to implanting the prosthetic heart valve and subsequently to inflating the balloon, providing temporary valve function by function of the temporary prosthetic valve leaflets. 